Registration Dossier

Administrative data

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-09-17 - 2018-10-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to a guideline study and under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: waxy solid
Details on test material:
- Name of test material (as cited in study report): CYPHOS 443

In vitro test system

Test system:
human skin model
Details on test system:
SOURCE AND COMPOSITION OF MEMBRANE BARRIER USED
- Was the Corrositex® test kit used: yes
- Components: hydrated collagen matrix (bio-barrier) on a supporting filter membrane and CDS, an underlying aqueous solution of two pH indicator dyes.

WAS THE COMPATIBILITY TEST PERFORMED: yes
Prior to performing the membrane barrier penetration study, Tetra-n-butyl-phosphonium chloride was evaluated for the compatibility with the CDS.
Tetra-n-butyl-phosphonium chloride (100 mg) 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®.

WAS THE TIMESCALE CATEGORY TEST PERFORMED: yes
Tetra-n-butyl-phosphonium chloride 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. Tetra-n-butyl-phosphonium chloride (100 mg) 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. In case no color change was observed in both buffers a conformation test was performed. Two drops of confirm reagent were added to buffer B. 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: room-temperature

METHOD OF APPLICATION:
Tetra-n-butyl-phosphonium chloride was applied (approximately 500 mg), directly on top of the bio-barrier. The test item was spread to match the size of the bio-barrier. Any residual volumes were discarded. All tests were performed at room temperature. The samples were at room temperature when applied.

NUMBER OF REPLICATES: 4

PREDICTION MODEL / DECISION CRITERIA
Determination of the UN Packing group or UN GHS subcategory -
Corrositex® penetration response time (minutes)
Timescale
Category 1 0 to 3 min. > 3 to 60 min. > 60 to 240 min. > 240 min.
Timescale
Category 2 0 to 3 min. > 3 to 30 min. > 30 to 60 min. > 60 min.
Group I or 1A Group II or 1B Group III or 1C Non-corrosive
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500mg

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 500 µl
- Concentration (if solution): 10%

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 500 mg
Number of replicates:
4

Results and discussion

In vitro

Results
Irritation / corrosion parameter:
penetration time (in minutes)
Remarks:
Mean penetration time (4 replicates)
Value:
41
Negative controls validity:
valid
Remarks:
> 60 min
Positive controls validity:
valid
Remarks:
18 min
Other effects / acceptance of results:
ACCEPTANCE OF RESULTS:
The test passed all acceptance criteria:
a) The negative control citric acid (10%) showed a mean penetration time of > 60 minutes and was therefore non-corrosive.
b) The positive control sodium hydroxide (as it is) breakthrough time (18 minutes) falls within ± two standard deviations of the positive control historical mean breakthrough time.
c) The positive control sodium hydroxide (as it is) showed a mean penetration time of 18 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, Tetra-n-butyl-phosphonium chloride is classified as UN packing group III (= GHS 1C) in the Corrositex® assay under the experimental conditions described in this report.
Executive summary:

The objective of this study was to evaluate Tetra-n-butyl-phosphonium chloride in the in vitro membrane barrier test for skin corrosion using Corrositex®. 

For this purpose Tetra-n-butyl-phosphonium chloride was topically applied on top of a bio-barrier and the ability of Tetra-n-butyl-phosphonium chloride to pass through a bio-barrier and to elicit a color change in the underlying liquid chemical detection system was evaluated.

The study procedures described in this report were based on the most recent OECD 435 guideline.

The test item compatibility test showed that Tetra-n-butyl-phosphonium chloride was compatible with the chemical detection system. Based on the acid or alkali reserve of the chemical the test item was classified as a timescale 2 compound. Tetra-n-butyl-phosphonium chloride (approximately 500 mg) was applied on top of the bio-barrier matrix. The elapsed time between application and penetration was determined by monitoring changes in the chemical detection system. 

Since Tetra-n-butyl-phosphonium chloride was a timescale 2 test item and showed a mean penetration time of 41 minutes, Tetra-n-butyl-phosphonium chloride is classified in III (= GHS 1C).