Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 29 Jan 2021 (Study Plan) to 23 Feb 2021 (Final Report)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
This in vivo study is required by regulatory authorities for registration in a non EU region. An in vitro skin irritation study in the EPISKIN model performed by NOTOX B.V. (Project 493070) showed that the test item was non-irritant to skin and confirms that the test item is non-corrosive. The pH of the test item was determined at the Pharmacy of Charles River Laboratories Hungary Kft. and found to be 5.38. This was within the acceptable range given by the OECD guideline (If the pH is 2 or less or 11.5 or greater, the study will not be conducted), therefore the test item was permitted to use in this study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021
Report date:
2021

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
barium(2+) dichloride dihydrate
EC Number:
600-412-6
Cas Number:
10326-27-9
Molecular formula:
BaCl2.2(H2O)
IUPAC Name:
barium(2+) dichloride dihydrate
Test material form:
solid: crystalline
Details on test material:
Name: Barium chloride dihydrate
Batch/Lot number: MSC0431
Purity: treated as 100%
Expiry date: 07 December 2021
Storage conditions: Controlled room temperature (15-25°C, ≤70% relative humidity), protected from humidity (tight closed container)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: 11 weeks
- Weight at study initiation: body weights were 2907-3008 g at dosing
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Dumbbell Device were used as an additional enrichment.
- Diet: Standard diet for rabbits produced by Cargill Takarmány Zrt, ad libitum
- Water: Free access to tap water.
- Acclimation period: 11 days before start of treatment under the same controlled environment conditions as during the experimental period. At least prior to dosing, it was ensured that the animals were healthy and that the skin to be treated was intact and free from any abnormality.

ENVIRONMENTAL CONDITIONS
- Temperature: 18.2 - 22.6°C (target: 20 ± 3°C
- Humidity: 48 - 69% (target 30 - 70%)
- Air changes: 15-20 air exchanges/hour
- Photoperiod: 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 02 Feb 2021 To: 23 Feb 2021.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
Amount(s) applied: An amount of 0.5 g of the test item (pulverised) was applied. The test item was moistened with an appropriate amount of water, sufficient to ensure good contact with the skin using a syringe.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 males
Details on study design:
TEST SITE
Approximately 24 hours prior to the test the hair was clipped from the back and flanks of the animals.The test item was applied to an area of approximately 6 cm² of intact skin. Sterile gauze pads were placed on the skin of rabbits. These gauze pads were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunk of the animals were then wrapped with plastic wrap held in place with an elastic stocking for 4 hours.

REMOVAL OF TEST SUBSTANCE
Four hours after application, the bandaging was removed and the any residual test item was removed by gently washing the skin with body temperature water.

OBSERVATION TIME POINTS
For ethical reasons, a single animal was treated with the test item first. One hour after application of the test item to the skin, the application site was examined. As neither a corrosive effect nor a severe irritant effect was observed at one hour, the bandage was replaced and the exposure was continued for a further 3 hours (a total 4-hour exposure). The initial animal was observed for signs of erythema and oedema immediately after patch removal. The test was completed using the 2 remaining animals.

Mortality/Viability: observation twice daily (at the beginning and end of each working day).
Clinical observations: any clinical signs of toxicity or signs of ill-health during the study was recorded daily.
Body Weights: body weights were recorded at the beginning and at the end of the observation period.
Irritation: Animals were examined for signs or effects of the test item. The degree of irritation was evaluated at 1 (± 5 min), 24 (± 30 min), 48 and 72 hours (± 60 min) following the patch removal. No sign of irritation was observed at 72 hours; therefore, the study was terminated. The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

SCORING SYSTEM:

Erythema and eschar formation:
No erythema ......................................................................................................................0
Very slight erythema (barely perceptible) ............................................................................. 1
Well defined erythema ....................................................................................................... 2
Moderate to severe erythema .............................................................................................. 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) ........................... 4

Oedema formation:
No oedema ..........................................................................................................................0
Very slight oedema (barely perceptible) ................................................................................. 1
Slight oedema (edges of area well-defined by definite raising) .................................................. 2
Moderate oedema (raised approximately 1 millimeter) ............................................................ 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure)........ 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all the 3 animals showed the same score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
first reading at 1h
Irritation parameter:
edema score
Basis:
mean
Remarks:
all the 3 animals showed the same score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
first reading at 1h
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
Irritation: No skin irritation was caused by 4 hours exposure to Barium chloride dihydrate
Corrosion: There was no evidence of a corrosive effect on the skin.
Toxicity / Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Other effects:
No histopathology was performed.

Any other information on results incl. tables

Deviations:

There were two protocol deviations in the study. The title of 18.1. Justification of Test System and Number of Eyes section in the Study Plan was mistyped, the correct title is: Justification of Test System.

The initial animal was observed for signs of erythema and oedema immediately after patch removal; however, this activity was not mentioned in the Study Plan.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Barium chloride dihydrate does not have to be classified for skin irritation according to the CLP and the UN GHS.
Executive summary:

The primary skin irritation/corrosion of Barium chloride dihydrate in the rabbit (4-hour semi-occlusive application) was investigated in a study performed according to the OECD Testing Guideline No.404 and under GLP.

Three young adult New Zealand rabbits were treated by topical application of 0.5 g test item to their intact shaved dorsal area. The duration of treatment was 4 hours. The scoring of skin reactions was performed at approximately 1, 24, 48 and 72 hours after removal of the dressing. The primary irritation index was calculated by totalling the mean cumulative scores at 24, 48 and 72 hours and then dividing by the number of data points.

No mortality occurred during the study and no clinical signs were observed. No local dermal signs were observed in the treated animals throughout the study and the primary irritation index was 0.00. The body weights of all rabbits were considered to be within the normal range of variability. As no clinical signs were observed at 72 hours after patch removal, the study was terminated after 72 hours of observation.

Under the conditions of this study barium chloride dihydrate is considered to be "non-irritant" to rabbit skin.