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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 15, 2016 - March, 10, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Dabeer S.A. (Batch/Lot No. 4140Z0925)
- Expiration date of the lot/batch: September, 25, 2018
- Purity test date: 2015-11-16


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in a cool well ventilated place
- Stability under test conditions: stable
- pH: 6.77
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
- Name of test material (as cited in study report): DABQUEL COMPLEX CaL
- Substance type: complex
- Physical state: brown liquid
- Composition of test material, percentage of components:
Calcium complexed content: 6.10%
Total Calcium content: 6.11%
- Lot/batch No.: 4140Z0925
- Expiration date of the lot/batch: September 25, 2018
- Storage condition of test material:
Storage Temperature: Room temperature
Storage Container: Keep container tightly closed in a dry, cool and well ventilated place
Storage Location : Test Item Control Office, JRF

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation, India
- Age at study initiation: 16 to 18 weeks
- Weight at study initiation: Minimum: 2.613, Maximum: 2.824
- Housing: individually in stainless steel wire meshed cages were used.
- Diet (e.g. ad libitum): Teklad certified Global High Fiber Rabbit pellet Feed manufactured by Harlan, USA ad libitum
- Water (e.g. ad libitum): UV sterilised drinking water filtered through Kent Reverse Osmosis water filtration system ad libitum
- Acclimation period: 7 to 9 days

Animal Identification
Each rabbit was uniquely numbered on the ear using a tattoo machine. Appropriate labels were attached to the cages indicating the study number, test item code, sex, dose, type of study, cage number and animal number.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23 °C
- Humidity (%): 63 to 65%
- Air changes (per hr): minimum 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 h artificial light and 12 h darkness, light hours being 06:00 - 18:00 h

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution):
Duration of treatment / exposure:
4 hours
Observation period:
The skin reactions of each rabbit were observed at 1, 24, 48 and 72 h post patch removal.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- % coverage:
- Type of wrap if used: gauze patch that was secured at the margins by non-irritating tape for a period of 4 h

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 4 h exposure period, the residual test item was removed with cotton soaked in distilled water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Irritation was scored according to OECD 404.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Irritant / corrosive response data:
There were no signs of systemic adverse effect in any treated rabbits.
Erythema was evident at 1 h in all rabbits which resolved by 24 h post patch removal in all rabbits. The mean dermal irritation scores at 24, 48 and 72 h post-patch removal for individual animals were 0.00, 0.00, 0.00 for erythema and 0.00, 0.00, 0.00 for oedema, respectively. No sign of skin irritation was observed throughout the experimental period.

Any other information on results incl. tables

Mean Dermal Irritation Score

The mean dermal irritation scores at 24, 48 and 72 h post-patch removal for animal Nº 1, 2 and 3 were 0.00, 0.00, 0.00 for erythema and 0.00, 0.00, 0.00 for oedema, respectively (TABLE 2).

Narrative Description of Skin Reactions

Following the 4 h exposure period (day 0), the skin of each rabbit was observed at 1, 24, 48 and 72 h post patch removal.

At 1 h post patch removal, the treated skin site revealed very slight erythema (barely perceptible) in all three rabbits (TABLE 1).

At 24 h post patch removal, the treated skin site recovered completely and appeared normal in all three rabbits throughout the experimental period (TABLE 1).

The control skin sites of all three rabbits were normal with no erythema and no oedema observed throughout the experimental period (TABLE 1).

Clinical Observations other than Dermal Irritation

No clinical signs were observed in any rabbit throughout the experimental period (APPENDIX 1).

Interpretation of Results

The mean scores of erythema (0.00) and oedema (0.00) observed at the 24, 48 and 72 h post patch removal observation time-points indicated that the DABQUEL COMPLEX CaL is a non-irritant under the described experimental conditions (TABLE 2).

Acute Dermal Irritation Study of DABQUEL COMPLEX CaL in Rabbits

TABLE1: Dermal Irritation Scores 

Control Site: Untreated                                                                                                    Sex: Male

Rabbit N°

Site of Application

Observations after Patch Removal

Erythema

Oedema

Hour

Hour

1

24

48

72

1

24

48

72

1

Right

0

0

0

0

0

0

0

0

2

Right

0

0

0

0

0

0

0

0

3

Right

0

0

0

0

0

0

0

0

 

Treated Site: 0.5 mL DABQUEL COMPLEX CaL (undiluted)

Rabbit N°

Site of Application

Observations after Patch Removal

Erythema

Oedema

Hour

Hour

1

24

48

72

1

24

48

72

1

Left 

1

0

0

0

0

0

0

0

2

Left

1

0

0

0

0

0

0

0

3

Left

1

0

0

0

0

0

0

0

Note: Refer section 2.12 for Irritation Scores


Acute Dermal Irritation Study of DABQUEL COMPLEX CaL in Rabbits

APPENDIX1: Clinical Observations and Body Weight (kg) of Individual Rabbit

Sex: Male

Rabbit

Clinical Observations made on Day

Body Weights (kg)

0

1

2

3

Before Treatment

At

Termination

1

1

1

1

1

2.824

2.887

2

1

1

1

1

2.613

2.692

3

1

1

1

1

2.739

2.801

Key:               0 = Day of dermal application

Clinical Sign:  1 = Normal

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2015), DABQUEL COMPLEX CaL is not classified as a skin irritant
Executive summary:

In an acute dermal irritation study, three adult male New Zealand White rabbits were dermally exposed to 0.5 mL DABQUEL COMPLEX CaL (undiluted), for 4 h (day 0), applied to approximately 6 cm² area of skin. Initially one rabbit was tested with a single patch applied evenly to the intact skin for a period of 4 h. Based on the observations at 24 h post patch removal, two additional rabbits were tested simultaneously to confirm the irritation response. The control skin site of each rabbit was untreated. The treated and the control sites were covered with a gauze patch that was secured at the margins by non-irritating tape for a period of 4 h. At the end of the 4 h exposure period, the residual test item was removed with cotton soaked in distilled water. The skin reactions of each rabbit were observed at 1, 24, 48 and 72 h post patch removal. Irritation was scored according to OECD 404.

There were no signs of systemic adverse effect in any treated rabbits.

Erythema was evident at 1 h in all rabbits which resolved by 24 h post patch removal in all rabbits. The mean dermal irritation scores at 24, 48 and 72 h post-patch removal for individual animals were 0.00, 0.00, 0.00 for erythema and 0.00, 0.00, 0.00 for oedema, respectively. No sign of skin irritation was observed throughout the experimental period.

Based on the results of this study, an indication of the classification for DABQUEL COMPLEX CaL is as follows:

Globally Harmonized System of Classification and Labeling of Chemicals (GHS 2015): Not classified as a skin irritant