Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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.
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)
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.
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
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.

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.

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.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-04-26 to 2010-06-07
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions
Qualifier:
according to guideline
Guideline:
other: OECD Guidelines for Testing of Chemicals, Draft Proposal for a New Guideline: In vitro skin irritation: Reconstructed Human Epidermis (RhE) Test method
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Commission regulation (EC) No. 440/2008 B.46
Deviations:
no
GLP compliance:
yes
Test system:
human skin model
Source species:
human
Cell type:
other: Adult human-derived epidermal keratinocytes
Cell source:
other: three-dimensional human epidermis model
Justification for test system used:
The EPISKIN model has been validated for irritation testing in an international validation study and its use is recommended by the relevant OECD guideline for irritation testing and therefore, it was considered to be suitable for this study.
Vehicle:
unchanged (no vehicle)
Details on test system:
TEST SYSTEM
EPISKIN Standard Model TM (EPISKIN-SM TM, 0.38 cm2, Lot no.: 10-EKIN-020; Source: SkinEthic Laboratories, Nice, France).
This model is a three-dimensional human epidermis model, which consists of adult human-derived epidermal keratinocytes which have been seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. The keratinocytes were cultured for 13 days, which results in a highly differentiated and stratified epidermis model comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum.

TEST FOR REDUCTION OF MTT BY THE TEST SUBSTANCE
Barium chloride was checked for possible direct MTT reduction before the study was started. To assess the ability of the test substance to reduce MTT, approximately 10 mg of test substance was added to a 12 well plate filled with 2 ml MTT solution (0.3 mg/ml in PBS). The mixture was incubated for approximately 3 hours at 37 °C. A negative control, sterile Milli-Q water was tested concurrently. Because no colour change was observed it was concluded that barium chloride dihydrate did not interact with MTT.

APPLICATION/TREATMENT OF THE TEST SUBSTANCE
The test was performed on a total of 3 tissues per test substance together with a negative control (Phosphate buffered saline (PBS, Invitrogen Corporation, Breda, the Netherlands) and a positive control (5% (aq) Sodium dodecyl sulphate (SDS, Sigma Aldrich, Zwijndrecht, The Netherlands, CAS Number 151-21-3). At least 10 mg solid (with a small glass weight boat) with 5 µl Milli-Q water (Millipore Corp., Bedford, Mass., U.S.A.) was added into 12-well plates on top of the skin tissues. Three tissues were treated with 10 µl PBS (negative control) and 3 tissues with 10 µl 5% SDS (positive control) respectively. The positive control was re-spread after 7 minutes contact time. After the exposure period of 15 minutes at room temperature, the tissues were washed with phosphate buffered saline to remove residual test substance. After rinsing the cell culture inserts were each dried carefully. The skin tissues were kept in new 12-well plates on 2 ml pre-warmed maintenance medium until all tissues were dosed and rinsed. Subsequently the skin tissues were incubated for 42 hours at 37 °C.

CELL VIABILITY MEASUREMENT
After incubation, cell culture inserts were dried carefully to remove excess medium and were transferred into a 12-wells plate prefilled with 2 ml MTT-medium (0.3 mg/ml). The tissues were incubated for 3 h at 37 °C. After incubation the tissues were placed on blotting paper to dry the tissues. Total biopsy was made by using a biopsy punch. Epidermis was separated from the collagen matrix and both parts were placed in prelabeled microtubes and extracted with 500 µl isopropanol (Merck, Darmstadt, Germany). Tubes were stored refrigerated and protected from light for 70 hours. The amount of extracted formazan was determined spectrophotometrically at 570 nm in duplicate with the Multiskan Spectrum (Thermo Labsystems).
Cell viablity was calcuated for each tissue as a percentage of the mean of the negative control tissues. Skin irritation potential of the test substance was classified according to remaining cell viability following exposure of the test substance.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): At least 10 mg of the solid test substance was applied directly on top of the skin tissue. Barium chloride was spread to match the size of the tissue.

VEHICLE
- Amount(s) applied (volume or weight with unit): Skin tissue was moistened with 5µl of Milli-Q water (Millipore Corp., Bedford, Mass., USA) to ensure close contact to the tissue.
Duration of treatment / exposure:
15 minutes
Duration of post-treatment incubation (if applicable):
42 hours
Number of replicates:
3 tissues
Details on test animals or test system and environmental conditions:
Not applicable - Since this is an in vitro study there is no information on test animals.
Vehicle:
water
Irritation / corrosion parameter:
% tissue viability
Value:
80
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation

TEST FOR REDUCTION OF MTT BY THE TEST SUBSTANCE

Because no colour change was observed it was concluded that barium chloride dihydrate did not interact with MTT.

Results after treatment with test substance:

Table 1. Individual OD measurements at 570 nm

 

A

(OD570)

B

(OD570)

C

(OD570)

Negative control

OD570measurement 1

OD570measurement 2

 

0.901

0.877

 

0.884

0.875

 

0.897

0.870

Barium chloride dihydrate

OD570measurement 1

OD570measurement 2

 

0.734

0.574

 

0.733

0.738

 

0.747

0.738

Positive control

OD570measurement 1

OD570measurement 2

 

0.050

0.056

 

0.061

0.063

 

0.069

0.067

OD = Optical density

Triplicate exposures are indicated by A, B and C.

The mean absorption at 570 nm measured after treatment with barium chloride dihydrate and controls are presented in Table 2.

Table 2.  Mean absorption in the in vitro skin irritation test with barium chloride dihydrate 

 

A

(OD570)

B

(OD570)

C

(OD570)

Mean

(OD570)

SD

Negative control

0.889

0.879

0.883

0.884

0.005

Barium chloride dihydrate

0.654

0.735

0.742

0.711

0.049

Positive control

0.053

0.062

0.068

0.061

0.008

 

OD = optical density

SD = Standard deviation

Triplicate exposures are indicated by A, B and C.

In this table the values are corrected for background absorption. Isopropanol was used to measure the background absorption.

 

Table 3 shows the mean tissue viability obtained after 15 minutes treatment with barium chloride dihydrate compared to the negative control tissue.

Table 3. Mean tissue viability in the in vitro skin irritation test with barium chloride dihydrate 

 

Mean tissue viability (percentage of control)

Negative control

100

Barium chloride dihydrate

80

Positive control

7

The positive control had a mean cell viability after 15 minutes exposure of 7 %.

Interpretation of results:
GHS criteria not met
Conclusions:
It is concluded that this test is valid and that barium chloride dihydrate is non-irritant in the in vitro skin irritation test under the experimental conditions described in this report.
Executive summary:

An in vitro skin irritation test of Barium chloride was performed in a reconstructed human epidermis model EPISKIN (SM). Disks of EPISKIN (three units) were treated with the test item and incubated for 15 minutes at room temperature. Exposure of the test item was terminated by rinsing with Phosphate Buffered Saline (PBS). The epidermis units were then incubated at 37°C for 42 hours in an incubator with 5% CO2. The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution in an incubator with 5% CO2 protected from light. The precipitated formazan crystals were then extracted using acidified isopropanol and quantified spectrophotometrically.

PBS and 5% (w/v) Sodium Dodecyl Sulphate (SDS) solution treated epidermis were used as negative and positive controls, respectively (three units / control). For each treated tissue, the viability was expressed as a % relative to the negative control. If the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal (≤) to 50% of the negative control, the test item is considered to be irritant to skin.

Following exposure with Barium carbonate, the mean cell viability was 80% compared to the negative control. This is above the threshold of 50%, therefore the test item was considered as being non-irritant to skin. The experiment met the validity criteria, therefore the study was considered to be valid.

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The toxicity of barium sulfate and barium chloride may reasonably be considered to be determined by availability of Ba2+cations. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Barium chloride is highly water soluble with ca. 375 g/L at pH ca. 6.5 (pH of artificial sweat solution), whereas barium sulfate is poorly soluble (3.1 mg/L at pH 9). Hence, any read across from barium chloride to BaSO4 is inherently very conservative.
Further information is included as attachment in Section 13.
Reason / purpose for cross-reference:
read-across source
Irritation / corrosion parameter:
% tissue viability
Value:
80
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Based on a read-across from Barium chloride dihydrate, the substance barium sulfate is considered as not irritating to skin.
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The toxicity of barium sulfate and barium chloride may reasonably be considered to be determined by availability of Ba2+cations. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Barium chloride is highly water soluble with ca. 375 g/L at pH ca. 6.5 (pH of artificial sweat solution), whereas barium sulfate is poorly soluble (3.1 mg/L at pH 9). Hence, any read across from barium chloride to BaSO4 is inherently very conservative.
Further information is included as attachment in Section 13.
Reason / purpose for cross-reference:
read-across source
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
Interpretation of results:
GHS criteria not met
Conclusions:
Based on a read-across from Barium chloride dihydrate, the substance barium sulfate is considered as not irritating to skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-08-03 to 2010-08-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
, 2002-04-24
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-11-12
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology GmbH & Co. KG, Branch Löhndorf, 24601 Löhndorf/Post Wankendorf, Germany
- Age at study initiation: Approx. 4.5 - 5.5 months
- Weight at study initiation: Animal 1: 2.5 kg; Animal 2: 2.5 kg; Animal 3: 2.4 kg
- Housing: For 8 hours following test item application, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excrements and urine. During the acclimatisation period and after the 8-hour period in restrainers, the animals were kept singly in cages with dimensions of 380 mm x 425 mm x 600 mm (manufacturer: Dipl.Ing. W. EHRET GmbH, 16352 Schönwalde, Germany).
- Diet (ad libitum): Commercial diet, ssniff7 K-H V2333 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum before and after the exposure period): Tap water
- Acclimation period: At least 20 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C +/- 3 °C (maximum range)
- Relative humidity: 30% - 70% (maximum range; aim was 50% - 60%)
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test item were administered into one eye each of three animals. The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.
No further information on the amount/concentration applied was stated.
Duration of treatment / exposure:
1 hour (One hour after application the eyes were rinsed.)
Observation period (in vivo):
1, 24, 48 and 72 hours after the administration
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
The test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further animals were employed 24 hours after start of the initial test.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were rinsed with portions of 20 mL 0.9 % aqueous NaCl solution, each.
- Time after start of exposure: 1 hour after administration

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48 and 72 hours after the administration. The eye reactions were observed and registered.
24 hours after administration, fluorescein (Fluorescein SE Thilo drops (ALCON PHARMA GmbH, 79108 Freiburg, Germany) was applied to the eyes before being examined to aid evaluation of the cornea for possible lesions.

OTHER OBSERVATIONS: Any further lesions not covered by the scoring system were recorded. Body weight of all animals was measured at the beginning of the study and at the end of the study. Behaviour and food consumption were monitored.
No further information on the study design was stated.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Conjunctival redness (grade 1 (Some blood vessels hyperaemic (injected)) was observed in all animals 1 hour after instillation. This effect was reversible after 24 hours.
In addition, secretion was observed in all animals 1 hour after instillation.
The cornea and the irises were not affected by instillation of the test item and the fluorescein test performed 24 hours after instillation did not reveal any changes.
Other effects:
There were no systemic intolerance reactions.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions barium sulphate - standard was non-irritating to eyes, hence, no labelling is required.
According to the EC Regulation 1272/2008 and subsequent regulations, the test item is non-irritating to eyes; no classification and labelling of the substance is necessary.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

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

Additional information

Respiratory tract irritation:

There are two reports of workers exposed chronically to barium sulfate dust demonstrated that this exposure had a minor effect on the lungs. The relevant robust study summaries are covered under the section repeated dose toxicity.

Justification for classification or non-classification

Skin irritation:

Reference Verbaan (2010) and Nagy (2021) are considered as the key studies for skin irritation and will be used for classification. Based on the results on the in vitro EPISKIN (SM) model test and the in vivo skin irritation study, barium sulfate is considered as non-irritant to skin. Therefore no classification for skin irritation is warrented according to Regulation (EC) 1272/2008 (CLP).

Eye irritation:

Reference Leuschner (2010) is considered as the key study for eye irritation and will be used for classification. The overall irritation results are as follows: Corneal opacity, iritis, conjunctival redness and conjunctival oedema, 24, 48 and 72h after application: mean score=0.0. The classification criteria according to regulation (EC) 1272/2008 as irritating to eyes are not met since the mean score after 24, 48 and 72h was 0.0, hence no classification required.

 

Respiratory irritation:

The classification as respiratory irritant is covered under the endpoint specific target organ toxicity- single exposure and repeated exposure. Please refer to the endpoint summaries on acute toxicity (endpoint 7.2) and repeated dose toxicity (endpoint 7.5) for further information.