Registration Dossier

Administrative data

Description of key information

Skin irritation: according to OECD 404, rabbit, undiluted, 4 h, semiocclusive, not irritating.
Eye irritation: according to OECD 405, rabbit, 1 % solution in distilled water, not irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
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)
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
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.
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.

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

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

 

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:
January 15, 2016 - March, 10, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well documented GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 16 to 17 weeks
- Weight at study initiation: Minimum: 2.561, Maximum: 2.741
- Housing: individually in stainless steel wire meshed cages
- 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: 8 - 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23 °C
- Humidity (%): 64 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 except light was kept ON at the time of the subcutaneous injection during night hours. Photoperiod was maintained through automatic timer.

Animal Identification
Each rabbit was serially numbered on the ear using a tattoo machine on day 1 of acclimatisation. Appropriate labels were attached to the cages indicating the study number, test item code, sex, dose, type of study, cage number and animal number.
Vehicle:
other: distilled water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 1 % solution in distilled water

VEHICLE
- Amount(s) applied (volume or weight with unit): distilled water, test item solved in it
- Concentration (if solution): 1 %
Duration of treatment / exposure:
8 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with 0.9 % normal saline
- Time after start of exposure: 24 after treatment

SCORING SYSTEM: according to OECD 405

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritant / corrosive response data:
Conjunctival redness was evident at 1 h in all three rabbits which resolved by 24 h post test item application (TIA). Conjunctival chemosis was evident at 1 h in rabbit N° 1 which was resolved by 24 h post TIA. The individual animal mean eye irritation scores of the 24, 48 and 72 h post TIA observation were 0.00, 0.00, 0.00 for corneal opacity, 0.00, 0.00, 0.00 for iris effects, 0.00, 0.00, 0.00 for conjunctival redness and 0.00, 0.00, 0.00 for conjunctival chemosis for rabbit N° 1, 2 and 3, respectively.

Mean Eye Irritation Scores

The individual animal mean eye irritation scores observed for corneal opacity (0.00), iritis (0.00), conjunctival redness (0.00) and conjunctival chemosis (0.00) following grading at 24, 48 and 72 h post TIA.

 

Narrative Description of Eye Irritation

 

Treated Eye

At 1 h post TIA, the treated eyes revealed conjunctival redness [some blood vessels definitely hyperaemic (injected) in all three rabbits; score of 1] and conjunctival chemosis [some swelling above normal (includes nictitating membranes) in rabbit N° 1; score of 1].

At 24 h post TIA, the treated eyes of all three rabbits recovered completely and appeared normal throughout the experimental period.

Examination with fluorescein dye and cobalt blue filter [corneal epithelium damage showing as green fluorescein staining] revealed no (area) corneal epithelium damage in all three rabbits at 24 h post TIA.

Corneal opacity and Iritis were not observed in all three rabbits throughout the experimental period.

 

Control Eye

No abnormalities were detected in the control eye of each rabbit during the course of this study (Table 3). No corneal epithelium damage was observed during the examination with fluorescein dye and cobalt blue filter.

 

Clinical Observations other than Eye Irritation

Other than eye irritation, no signs of systemic toxicity including clinical observation and body weight were observed in the rabbits throughout the experimental period.

 

Interpretation of Results

Conjunctival redness was evident at 1 h in all three rabbits which resolved by 24 h post TIA. Conjunctival chemosis was evident at 1 h in rabbit N° 1 which was resolved by 24 h post TIA. The individual animal mean eye irritation scores of the 24, 48 and 72 h post TIA observation were 0.00, 0.00, 0.00 for corneal opacity, 0.00, 0.00, 0.00 for iris effects, 0.00, 0.00, 0.00 for conjunctival redness and 0.00, 0.00, 0.00 for conjunctival chemosis for rabbit N° 1, 2 and 3, respectively.

 

Conclusion

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 Labelling of Chemicals (GHS 2015): Not classified as an eye irritant

Acute Eye Irritation Study of DABQUEL COMPLEX CaL in Rabbits 

TABLE1: Mean Eye Irritation Scores

Sex: Female

Rabbit N°

Mean Score at 24, 48 and 72 Hours

Opacity: Degree of Density

Iris Lesion

Conjunctivae

Redness

Chemosis

1

0.00

0.00

0.00

0.00

2

0.00

0.00

0.00

0.00

3

0.00

0.00

0.00

0.00

Acute Eye Irritation Study of DABQUEL COMPLEX CaL in Rabbits 

Table 2: Clinical Observations (Non Ocular) and Body Weight (kg) of Individual Rabbit 

A. Clinical Observation (Non Ocular)                                                                         

Sex:Female

Rabbit

Observations made on Day

0

1

2

3

1

1

1

1

1

2

1

1

1

1

3

1

1

1

1

Key:  0 = Day of treatment

          1 = Normal

B. Body Weight Record

Rabbit N°

Body Weight (kg)

Initial (Day 0)

Termination (72 h)

1

2.561

2.598

2

2.720

2.939

3

2.741

2.813

Acute Eye Irritation Study of DABQUEL COMPLEX CaL in Rabbits 

Table 3 :Individual Scores of Eye Reactions Post Application 

Control Eye                                                                                                                   

Sex: Female

Rabbit N°

1

2

3

Site of Application

Left

Left

Left

Reaction

Hour

Hour

Hour

1

24

48

72

1

24

48

72

1

24

48

72

Opacity:

Degree of Density

0

0

0

0

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctivae

(Redness)

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctivae

(Chemosis)

0

0

0

0

0

0

0

0

0

0

0

0

 Treated Eye

Rabbit N°

1

2

3

Site of Application

Right

Right

Right

Reaction

Hour

Hour

Hour

1

24

48

72

1

24

48

72

1

24

48

72

Opacity:

Degree of Density

0

0

0

0

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctivae

(Redness)

1

0

0

0

1

0

0

0

1

0

0

0

Conjunctivae

(Chemosis)

1

0

0

0

0

0

0

0

0

0

0

0

Acute Eye Irritation Study ofDABQUEL COMPLEX CaLin Rabbits

Table 4: Individual Corneal Observations 24 h Post Application using Fluorescein Dye Staining 

Control Eye                                                                                                                   

Sex: Female

Rabbit N°

Control Eye

Fluorescein Staining Response

Details of Corneal Damage

Observed in Control Eye

1

Left

Negative

No corneal epithelium damage was observed.

2

Left

Negative

No corneal epithelium damage was observed.

3

Left

Negative

No corneal epithelium damage was observed.

Treated Eye

Rabbit N°

Treated Eye

Fluorescein Staining Response

Details of Corneal Damage

Observed in Treated Eye

1

Right

Negative

No corneal epithelium damage was observed.

2

Right

Negative

No corneal epithelium damage was observed.

3

Right

Negative

No corneal epithelium damage was observed.

Acute Eye Irritation Study of DABQUEL COMPLEX CaL in Rabbits

 Table 5:Details of Injections and Applications 

Rabbit

On

Day

Administration of Systemic Analgesics

(Subcutaneous Injection)

Administration of Topical Anaesthetic

(1 to 2 drops)0.5% Proparacaine Hydrochloride

Time of Test Item

Application (0.1 mL)

Buprenorphine hydrochloride

(0.01 mg/kg body weight)

Meloxicam

(0.5 mg/kg body weight)

1

0

11:30 am and 8:50 pm

8:50 pm

12:25 pm

12:30 pm

1

8:42 am

-

-

-

2 and 3

0

11:47 am to 11:48 am and

8:49 pm to 8:50 pm

8:49 pm

to

8:50 pm

12:42 pm

to

12:43 pm

12:47 pm

to

12:48 pm

1

8:53 am to 8:54 am

-

-

-

Key : - = Not applicable

Note: Day 0 = Day of treatment

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Examination with fluorescein dye and cobalt blue filter at 24 h post test item application revealed no corneal epithelium damage in all rabbits. 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 Labelling of Chemicals (GHS 2015): Not classified as an eye irritant
Executive summary:

In an acute eye irritation study, 3 adult male New Zealand White rabbits were given a single ocular application of 0.1 mL DABQUEL COMPLEX CaL in the right eye of the rabbit while the contralateral eye remained untreated and served as the control. Initially one rabbit was tested. Based on the results obtained at 24 h post Test Item Application (TIA), the irritation response was confirmed by testing two additional rabbits simultaneously. Observations were made at 1, 24, 48 and 72 h post TIA. General health status was also checked.

Conjunctival effects were evident at 1 h in all three rabbits which resolved by 24 h post TIA. The animal mean eye irritation scores of the 24, 48 and 72 h post TIA observation were 0.00, 0.00, 0.00 for corneal opacity, 0.00, 0.00, 0.00 for iris effects, 0.00, 0.00, 0.00 for conjunctival redness and 0.00, 0.00, 0.00 for conjunctival chemosis for rabbit N° 1, 2 and 3, respectively.

Examination with fluorescein dye and cobalt blue filter at 24 h post TIA revealed no corneal epithelium damage in all rabbits.

The control eye did not show any abnormal reaction during the study. Moreover, there were no signs of systemic toxicity in any animal observed.

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 Labelling of Chemicals (GHS 2015): Not classified as an eye irritant

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

Additional information

Skin irritation

The skin irritation potential of Calcium glucoheptonate (CAS 1821694-25-0) was tested in vivo in rabbits (Patel, 2016A, acc. OECD 404).

For this acute dermal irritation study, three adult male New Zealand White rabbits were dermally exposed to 0.5 mL DABQUEL COMPLEX CaL (undiluted, Calcium complexed content 6.10 %), 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.

 

In addition to this, primary dermal irritation tests with 0.5 ml of the 50% solution of gluconic acid (pH: 1.8) in 12 albino rabbits demonstrated, that – as all the effects have cleared up after a 72 hours observation period – the test substance is not a dermal irritant (TNO, 1984, cited in OECD SIDS, 2004).

Moreover, the 2014 Cosmetic Ingredient Review Expert Panel acknowledged that the group of monosaccharides, disaccharides, and their related Ingredients, including calcium gluconate and gluconic acid, are safe for humans at concentrations as used in cosmetics. Based on the clinical experience of the Panel, there is little concern that these ingredients are irritants or sensitizers.

Eye irritation

The eye irritation potential of Calcium glucoheptonate (CAS 1821694-25-0) was tested in vivo in rabbits (Patel, 2016B, acc. OECD 405).

For this acute eye irritation study, 3 adult male New Zealand White rabbits were given a single ocular application of 0.1 mL DABQUEL COMPLEX CaL (undiluted, Calcium complexed content : 6.10%) in the right eye of the rabbit while the contralateral eye remained untreated and served as the control. Initially one rabbit was tested. Based on the results obtained at 24 h post Test Item Application (TIA), the irritation response was confirmed by testing two additional rabbits simultaneously. Observations were made at 1, 24, 48 and 72 h post TIA. General health status was also checked.

Conjunctival effects were evident at 1 h in all three rabbits which resolved by 24 h post TIA. The animal mean eye irritation scores of the 24, 48 and 72 h post TIA observation were 0.00, 0.00, 0.00 for corneal opacity, 0.00, 0.00, 0.00 for iris effects, 0.00, 0.00, 0.00 for conjunctival redness and 0.00, 0.00, 0.00 for conjunctival chemosis for rabbit N° 1, 2 and 3, respectively.

Examination with fluorescein dye and cobalt blue filter at 24 h post TIA revealed no corneal epithelium damage in all rabbits.

The control eye did not show any abnormal reaction during the study. Moreover, there were no signs of systemic toxicity in any animal observed.


Justification for selection of skin irritation / corrosion endpoint:
the only well documented GLP guideline study.

Justification for selection of eye irritation endpoint:
the only well documented GLP guideline study.

Justification for classification or non-classification

Based on the results of the available studies, Calcium glucoheptonate (CAS 1821694 -25 -0) is in accordance with European Regulation (EC) No. 1272/2008, does not meet criteria for classification and labelling as a skin or eye irritant.