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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-03-02 - 2018-03-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER))
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
Molecular Formula:
HOCH2C(Br)CH2OH
Molecular Weight:
245.91
Physical Appearance:
White crystalline powder
CAS No.:
3234-02-4
Batch Number:
1088
Purity:
100%

In vitro test system

Test system:
isolated skin discs
Source species:
rat
Cell type:
non-transformed keratinocytes
Cell source:
other: skin discs obtained from humanely sacrificed rats
Source strain:
Wistar
Details on animal used as source of test system:
Species:
Rat (Rattus norvegicus)
Strain:
Wistar
Justification of selection:
Rat is the rodent species and Wistar is the strain recommended by the test guideline.
Source:
Bred and reared at INTOX PVT. LTD.
Age at start of study:
22 days
No. of animals and sex:
5 males
Vehicle:
water
Details on test system:
Animals were humanely sacrificed by CO2 asphyxiation, when they was 28 days old. The dorso-lateral skin of each animal was then removed and stripped of excess subcutaneous fat by peeling it away from the skin. Skin discs, with a diameter of approximately 20 mm each, were prepared using scissors. As many as 4-5 skin discs were obtained from a single rat skin.
Control samples:
yes, concurrent vehicle
yes, concurrent positive control
Amount/concentration applied:
150 mg + 150µL analytical grade water
Duration of treatment / exposure:
24 hours
Number of replicates:
3

Results and discussion

In vitro

Resultsopen allclose all
Irritation / corrosion parameter:
transcutaneous electrical resistance (in kΩ)
Run / experiment:
test item
Value:
16.17
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
dye content (µg/disc)
Run / experiment:
test item
Value:
40.12
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
transcutaneous electrical resistance (in kΩ)
Run / experiment:
neg. control
Value:
10.23
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
dye content (µg/disc)
Run / experiment:
neg. control
Value:
39.13
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
transcutaneous electrical resistance (in kΩ)
Run / experiment:
pos. control
Value:
1
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
dye content (µg/disc)
Run / experiment:
pos. control
Value:
92.38
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In-Vitro Skin Corrosion Study by Transcutaneous Electrical Resistance Test Method (TER) of trans-2,3-Dibromo-2-Butene-1,4-Diol was carried out in compliance with the Organization for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals, Section 4, No. 430 - In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER), adopted by the council on 26 July 2013.
The mean TER value obtained for test item trans-2,3-Dibromo-2-Butene-1,4-Diol was 16.17 K (which was greater than 5 k) and the skin discs showed no obvious damage (e.g. perforation). The mean disc dye content was 40.12 μg/disc, which was lesser than the mean disc dye content of the 10M HCl positive control obtained concurrently.
According to the criteria of acceptance, under the experimental conditions of the study 'In-Vitro Skin Corrosion Study by Transcutaneous Electrical Resistance Test Method (TER) of trans-2,3-Dibromo-2-Butene-1,4-Diol it is concluded that the test item trans-2,3-Dibromo-2-Butene-1,4-Diol is considered as non-corrosive to rat skin as per the United Nations(UN) Globally Harmonised System (GHS) for classification of chemicals.
Executive summary:

In-Vitro Skin Corrosion Study by Transcutaneous Electrical Resistance Test Method (TER) of trans-2,3-Dibromo-2-Butene-1,4-Diol, using Skin Discs of Rats was carried out in compliance with the Organization for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals, Section 4, No. 430 - In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER), adopted by the council on 26 July 2013 and as per mutually agreed study plan.

Trans-2,3-Dibromo-2-Butene-1,4-Diol, was evaluated for its corrosive potential by its ability to produce a loss of normal stratum corneum integrity and barrier function, which was measured as a reduction in the TER below the threshold level (cut-off value) of 5 k Ω for rat skin, and from any increase in the ionic permeability for sulforhodamine B dye.

The skin discs were taken from humanely sacrificed rats aged 28 days and were applied with 150 μL of test item, in triplicate. Concurrent triplicate sets of skin discs were applied either with analytical grade water (150 μl) as negative control or with 10M hydrochloric acid (150 μl) as positive control.

The test and control items were applied for up to 24 hours at 22 °C to the epidermal surfaces of skin discs in a two compartment test system in which the skin disc functioned as the separation between the compartments. The test / control items were then removed by washing with a jet of tap water until no further material could be removed. The skin impedance was measured as TER by using Aplab Autocompute LCR-Q meter 4910. The electrodes of LCR-Q meter were placed on either side of the skin disc to measure the resistance of skin disc at a frequency of 100 Hz and using series values. Following TER measurement, the skin was carefully examined for obvious damage. After visual examination, 10% (w/v) sulforhodamine B was applied to the epidermal surface of each skin disc for 2 hours, which was followed by the measurement of dye content in each skin disc.

The mean resistance of the skin in the negative control group was found to be 10.23 K Ω which was within the acceptable range of 10 to 25 k Ω and the mean dye content of skin disc was 39.13 μg/disc which was closer to the acceptable range of 15 to 35 μg/disc.

The mean resistance of the skin in the positive control group was found to be 1.00 K Ω which was within the acceptable range of 0.5 to 1.0 k Ω while the mean dye content of skin disc was 92.38 μg/disc, which was within the acceptable range of 40 to 100 μg/disc, thereby validating the experimental procedure.

The mean TER value obtained for trans-2,3-Dibromo-2-Butene-1,4-Diol was 16.17 K Ω which was greater than 5 k Ω, the skin discs showed no obvious damage (e.g. perforation) and mean disc dye content was found to be 40.12 μg/disc which was lesser than that observed in skin discs treated with the positive control item.

Under the given experimental conditions of this study, it is concluded that the test item trans-2,3-Dibromo-2-Butene-1,4-Diol is considered non-corrosive to skin of the rat.