Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Corrositex skin corrosion test: corrosive (BASF SE, 2012). RA to structurally similar 4-chlorobutyryl chloride, CAS 4635-59-0 (BASF AG, 1973), supporting the result
There are no data available concerning eye irritation.

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
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
GLP compliance:
yes (incl. QA statement)
Details on study design:
MATERIAL AND TECHNICAL EQUIPMENT:
- Corrositex kit: InVitro International, Irvine CA, USA, containing reagents required for qualification and categorization screen, biobarrier matrix powder and diluent, membrane discs and vials containing the Chemical Detection System.
- Fume hood: The assay is run in a fume hood.
- Pipettes / positive displacement pipette: 150 μL / 500 μL - for application of liquids.
- Weighing boat and scales: for weighing of solids (100 mg / 500 mg)
- Electronic time clocks: for determining the time until a reaction occurs

CONTROLS:
- Negative control (NC): 10% citric acid (Sigma-Aldrich, Germany)
- Positive control (PC): Sodium hydroxide (solid) (Merck, Germany)

TEST SYSTEM CORROSITEX ASSAY: The Corrositex assay is a standardized in vitro corrosion test. The Corrositex assay kit is commercially available from InVitro International. The Corrositex Biobarrier Membrane is a test system consisting of a reconstituted collagen matrix. The assay is based on the time that is required for the test substance to penetrate through the Corrositex Biobarrier 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 those materials which cause detectable pH changes in the CDS.

ANALYSES: No analysis of test-substance preparation was performed, because the test substance was applied undiluted.

EXPERIMENTAL PROCEDURE: The experimental design of this study consisted of a qualification screen with the CDS (to determine if a color change can be detected) and a categorization screen (to categorize weak acids/bases and strong acids/bases), which were performed as a pretest, and a definitive Corrositex assay. The Corrositex assay was evaluated on the basis of the color change of the CDS. The time that a color change was observed was recorded manually and the break through times of the four replicates was used to determine the corrosive potential of the test substance.
- Test substance compatibility with the assay (qualification screen): For the qualification screen, 150 μL of the test substance was added to the CDS screening tube. If the test substance failed to produce a color change in the CDS within one minute, the test substance could not be analyzed in this system, and no further testing was required.
- Categorization screen: The categorization screen was used to assess the appropriate scoring scale for the test substance. The categorization screen was performed by adding 150 μL of test substance to each tube A and B. Each tube was mixed and the resulting color observed. If required, 2 drops of the "confirm" reagent were added to tube B, the tube mixed, and the resulting color observed. The categorization kit and color chart provided by InVitro International were used to determine the category. The test substance resulting in category 1 (high acid/alkaline reserve) was scored using the timetable in row 1 of the evaluation scheme while category 2 (low acid/alkaline reserve) was scored using the timetable in row 2 of the evaluation scheme (see below).
- Biobarrier preparation: The vial containing the biobarrier matrix powder was placed in a water bath at 64 – 68ºC. The entire contents of the biobarrier diluent vial was added slowly to the matrix powder. The stir bar rotated slowly enough to avoid foaming of the solution. Two hundred μL of the solubilized matrix was pipetted into each of the membrane discs. The membrane discs were then refrigerated for at least 2 hours at 2 – 8ºC. The biobarriers were wrapped and stored at 2 – 8ºC for a maximum of 7 days. Any remaining matrix solution was stored at 2 – 8ºC for up to 30 days in order to prepare additional biobarrier membrane discs.
- 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 and NC, each. A membrane disc coated with the biobarrier matrix was placed into one vial containing the CDS and approximately 500 μL of the test substance was 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 (for evaluation scheme see table below) or until break through 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 positive control vial was prepared as described above and received one pellet of sodium hydroxide on top of the membrane disc. This vial was monitored continuously until break through had occurred. The negative control vial was prepared as described above and received 500 μL of 10% citric acid. This vial was observed for 60 minutes and was evaluated as “non-corrosive” if no reaction had been observed.

ACCEPTANCE CRITERIA: The Corrositex assay was accepted if the breakthrough time for the positive control substance was in the historic control range (mean ± 2-3 x standard deviation). To demonstrate the functional integrity of the membrane barrier, the acceptance criterium for the negative control was not to induce membrane breakthrough within a 60 min observation period.

EVALUATION OF RESULTS: Corrosive potential was determined on the basis of the average time recorded for the test substance to produce a change in the CDS. For evaluation scheme see table below.
Irritation / corrosion parameter:
other: other: Break Through Time
Remarks on result:
other: Basis: mean. Remarks: 14 minutes 13 seconds. (migrated information)
Irritant / corrosive response data:
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 1 (having a high acid/alkaline reserve).
In the main test four Corrositex® Biobarrier Membranes were treated with the undiluted test substance. The mean breakthrough time of the test substance, determined in the actual Corrositex® assay, was 14 minutes and 13 seconds.

FINDINGS:

Test Article

Break Through Time [min:s]

 

Vial 1

Vial 2

Vial 3

Vial 4

Mean

Test substance

14:34

14:43

13:20

14:13

14:13

Controls:

 

PC:

NaOH, solid

14:44

-

-

-

-

NC:

10% citric acid

NB

-

-

-

-

NB = no break through within maximum observation period (60 min)

 

HISTORICAL CONTROL DATA:

Historical period: Jun 2009 – Feb 2015

Number of studies performed: 54

 

Break through time of

 

mean

[min:s]

SD

[min:s]

PC (NaOH, solid)

11:47

2:23

NC (10% citric acid)

NB

-

NB = no break through within maximum observation period (60 min)

Interpretation of results:
corrosive
Remarks:
Migrated information
Conclusions:
Based on the observed results and applying the evaluation criteria it was concluded, that the test substance shows a corrosive potential in the Corrositex - Skin Corrosion Test under the test conditions chosen. The mean break through time determined in the in vitro membrane barrier test indicates that the test substance has an intermediate corrosive potential and should be assigned to UN GHS skin corrosivity subcategories 1B or UN Transport Packing Group II as specified in OECD TG 435 (adopted 19 July 2006).
Executive summary:

The study was performed according to OECD TG 435 in compliance with GLP.

The potential of the test substance to cause dermal corrosion was assessed by a single topical application of 500 μL of the test substance to the Corrositex Biobarrier Membrane (Corrositex assay). The Corrositex Biobarrier Membrane is the test system consisting of a reconstituted collagen matrix. The assay is based on the time that is required for the test substance to penetrate through the Corrositex Biobarrier Membrane and produce a change in the Chemical Detection System (CDS). In addition to the test substance a positive and a negative control were assessed.

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 1 (having a high acid/alkaline reserve). In the main test four Corrositex® Biobarrier Membranes were treated with the undiluted test substance. The mean breakthrough time of the test substance, determined in the actual Corrositex® assay, was 14 minutes and 13 seconds.

Based on the observed results and applying the evaluation criteria it was concluded, that the test substance shows a corrosive potential in the Corrositex - Skin Corrosion Test under the test conditions chosen. The break through time indicates that the test substance has an intermediate corrosive potential and should be assigned to UN GHS skin corrosivity subcategories 1B or UN Transport Packing Group II as specified in OECD TG 435 (adopted 19 July 2006).

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

Skin irritation/corrosion:

The key study was performed according to OECD guideline 435 in complinace with GLP (BASF SE, 2015). The potential of the test substance to cause dermal corrosion was assessed by a single topical application of 500 μL of the test substance to the Corrositex Biobarrier Membrane (Corrositex assay). The Corrositex Biobarrier Membrane is the test system consisting of a reconstituted collagen matrix. The assay is based on the time that is required for the test substance to penetrate through the Corrositex Biobarrier Membrane and produce a change in the Chemical Detection System (CDS). In addition to the test substance a positive and a negative control were assessed.

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 1 (having a high acid/alkaline reserve). In the main test four Corrositex Biobarrier Membranes were treated with the test substance. The mean break through time of the test substance, determined in the actual Corrositex assay, was 14 minutes and 13 seconds.

Based on the observed results and applying the evaluation criteria it was concluded, that the test substance shows a corrosive potential in the Corrositex - Skin Corrosion Test under the test conditions chosen.

Supportingly, an in vivo skin irritation/corrosion study in rabbits is available with the structurally similar substance 4 -chlorobutyryl chloride, CAS 4635 -59 -0 (BASF AG, 1973), demonstrating corrosive potential of the test substance.

Eye irritation/corrosion:

There are no data available. Nevertheless, the skin corrosive potential of 5 -chlorovalerylchloride suggests that the substance also causes severe damage to the eye.


Justification for selection of skin irritation / corrosion endpoint:
One in vitro skin corrosion study (Corrositex) is available. This study is a GLP OECD guideline study and adequate for covering this endpoint.

Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

The available experimental test data for skin irritation/corrosion are reliable and suitable for the purpose of classification under Regulation (EC) No. 1272/2008. The results of the Corrositex (BASF SE, 2015) indicate that the test substance has an intermediate corrosive potential and should be assigned to UN GHS skin corrosivity subcategory 1B. Accordingly, the substance is classified as corrosive to the skin and eye (Cat. 1B, H314, Causes severe skin burns and eye damage).

According to Annex VI of Directive 67/548/EWG the substance is classified as corrosive to the skin and eye (C, R34).

Categories Display