Registration Dossier

Administrative data

Description of key information

Skin irritation / corrosion: corrosive (OECD 404), Classification Cat. 1B (H314).
Eye irritation/corrosion: corrosive (OECD 438), Classification Cat. 1 (H318).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09/01/1991-12/02/1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 404)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.27-2.55 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Rabbit Diet, Preston farmers Limited, New Leake, Boston, Lincolnshire, UK)
- Water (e.g. ad libitum): ad libitum (drinking water)
- Acclimation period: minimum acclimasitation period of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21°C
- Humidity (%): 45-60%
- Air changes (per hr): approximately 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml of the test material


Duration of treatment / exposure:
4 hours exposure
3 minute exposure
Observation period:
Approximately 1, 24, 48 and 72 hours, 7 and 14 days following removal of the patches
Number of animals:
3 animals 4 hour exposure
3 animals 3 minute exposure
Details on study design:
TEST SITE
- Area of exposure: 0.5 ml of the test material was introduced under a 2.5 x 2.5 cm gauze patch and placed in position on the shorn skin
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: four hours, 3 minutes


SCORING SYSTEM: according to the scale from Draize J. H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 Hours exposure. Haemorrhage of dermal capillaries. Reaction extending beyond the site of application
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of erythema not possible due to other adverse reactions
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: haemorrhage of dermal capillaries. Reaction extending beyond the site of application
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of erythema not possible due to other adverse reactions
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Haemorrhage of dermal capillaries. Light brown discolouration of the epidermis. Reaction extending beyond the site of application
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of erythema not possible due to adverse reactions
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Reaction extending beyond the site of application
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of oedema not possible due to adverse reactions
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Reaction extending beyond the site of application
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of oedema not possible due to adverse reactions
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: 4 hours exposure. Reaction extending beyond the site of application
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours, 7 days
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 4 hours exposure. Evaluation of oedema not possible due to adverse reactions
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 1, 24, 48, 72 hours, 7 & 14 days
Score:
>= 0 - <= 2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure. 14 days: reduced regrowth of fur and desquamation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 1, 24, 48, 72 hours, 7 & 14 days
Score:
>= 0 - <= 2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure. 14 days: reduced growth of fur and desquamation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure. 14 days: reduce growth of fur and desquamation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 1, 24, 48, 72 h, 7 & 14 days
Score:
>= 0 - <= 4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 3 minute exposure
Irritant / corrosive response data:
4-hour exposure period:
Severe erythema and oedema was noted at all treated skin sites one after patch removal. The reaction extended up to 4 cm beyond all treatment sites during the study.

3-minute exposure period:
Well-defined or moderate to severe erythema was noted at all treated skin sites one, 24, and 48-hours after patch removal. Well-defined erythema continued to be noted at two treated skin sites at the 72-hour observation.
Moderate to severe oedema was noted at all treated skin sites one hour after patch removal. Slight to severe oedema was noted at the 24-hour observation with very slight to moderate oedema at the 72-hour observation. Very slight to slight oedema was noted at two treated skin sites at the 7-day observation. Ocasionally the reaction extended 2-3 cm beyond the treatment site.
Other effects:
4-hour exposure period:
Evaluation of the erythema and oedema was not possible at the 24, 48, 72-hour and 7 days observations due to other adverse reactions. These included haemorrhage of the dermal capilleries, hardened dark brown/black-coloured scabs, blanching, well-defined or moderate erythema surrounding the treatment site, undulating scabs, scabs lifting at edges to reveal either dried blood or light brown-coloured scabs with small areas of dried blood. These reactions were considered to be indicated of dermal corrosion.

3-minute exposure period:
Evaluation of the erythema and oedema was not possible at one treatment site at the 72-hour observation and at all treatment sites at the 7-day observation due to other adverse reactions. These included haemorrhage of the dermal capilleries, light brown discolouration of the epidermis, loss of skin elasticity, thickening of the skin, hardened dark/black-coloured scab, well-defined erythema surrounding the treatment site, hardened light brown-coloured scab, reduced re-growth of fur and desquamation.

Key to tables:

Hd = haemorrhage of dermal capilleries

St = hardened dark brown/black-coloured scab

Bl = blanching

We = well-defined erythema surrounding other skin reactions

Sw = undulating scab

Sb = scab lifting at edges to reveal dried blood

Sd = scab lifting to reveal further deep scabing

Sd* = dark brown/black-coloured scab has lifted to reveal a light brown-coloured scab with small areas of dried blood

?e = evaluation of erythema not possible due to other adverse reactions

?Od = evaluation of oedema not possible due to other adverse reactions

Br = light brown discolouration of the epidermis

Th = thickening of the skin

Le = loss of skin elasticity

Sp = hardened light brown-coloured scab

Fr = reduced regrowth of fur

D = desquamation

R = reaction extending beyond the site of application

Individual reactions for dermal irritation following 4 -hour exposure

Skin reactions 

Reading 

Individual Scores – Rabbit Number and Sex (Bodyweight Kg)

44 Female

(2.54)

53 Female

(2.55)

55 Female

(2.47)

Erythema/eschar formation 

1 h 

4HdR 

4HdR

4HdBrR

 

24 h 

?eStBlWeR

?eStMeR

?eStMeRBl

 

48 h 

?eStBiWeR 

?eStMeR

?eStMeR 

 

72 h 

?eStWeR 

?eStWeR

?eStWeR 

 

7 days 

?eStSwR

?eStSwSbR

?eSd*R

 

14 days 

-

-

-

Oedema formation 

1 h 

4R

4R

4R 

 

24 h 

?Od

?Od

?Od

 

48 h 

?Od

?Od

?Od

 

72 h 

?Od

?Od

?Od 

 

7 days 

?Od 

?Od 

?Od 

 

14 days 

-

-

-

Individual reactions for dermal irritation following 3 -minute exposure

Skin reactions 

Reading 

Individual Scores – Rabbit Number and Sex (Bodyweight Kg)

40 Female 

(2.30)

41 Female 

(2.40)

43 Female 

(2.27)

Erythema/eschar formation 

1 h 

2Hd 

2Hd 

3Hd 

 

24 h 

2HdBrR 

2HdBr 

3HdBr 

 

48 h 

2HdBrLeR 

2Br 

HdBrLeTh 

 

72 h 

2HdBrThLeR 

2BrLe 

?eStWeR 

 

7 days 

?eSp 

?eSp 

?eSt 

 

14 days 

0FrD 

0FrD 

0FrD 

Oedema formation 

1 h 

 

24 h 

 

48 h 

 

72 h 

?Od 

 

7 days 

?Od 

?Od 

?Od 

 

14 days 

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material phenol 2-(1-methylpropyl) was regarded as corrosive according to CLP classification.
Executive summary:

A study was perform to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC.

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced reactions indicative of corrosion. Adverse dermal reactions included haemorrhage of the dermal capillaries, blanching of the skin, scabbing, severe erythema and severe oedema.

A single 3 -minute, semi-occluded application of the test material to an additional group of three rabbits produced well-defined to severe erythema and very slight to severe oedema. Other adverse reactions noted were haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, loss of skin elasticity, thickening of the skin, scabbing, reduced re-growth of fur and desquamation.

The test material phenol 2-(1-methylpropyl) was regarded as corrosive.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The Isolated Chicken Eye (ICE) test is an in vitro method that can be used to identify chemicals inducing serious eye damage (Category 1 according to the United Nations (UN) Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures) as well as chemicals that do not require classification for eye irritation or serious eye damage as defined by UN GHS and Regulation (EC) No 1272/2008. The ICE test was evaluated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), in conjunction with the European Centre for the Validation of Alternative Methods (ECVAM) and the Japanese Centre for the Validation of Alternative Methods (JaCVAM) (2006 and 2010).
The purpose of this method is to describe the procedures involved to evaluate the eye hazard potential of a test chemical as measured by its ability to induce toxicity in an enucleated chicken eye. Toxic effects to the cornea are measured by (i) a qualitative assessment of opacity (ii) a qualitative assessment of damage to epithelium based on application of fluorescein to the eye (fluorescein retention) (iii) a quantitative measurement of increased thickness (swelling) and (iv) a qualitative evaluation of macroscopic morphological damage to the surface.
The ICE test can also be used to identify chemicals not requiring classification according to the UN GHS Classification System.
Preferred species of choice since the test was developed using this species and allows for comparison with in vivo eye irritation data and they are specified in the appropriate test guidelines.
Qualifier:
according to
Guideline:
OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
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: A00000035
- Expiration date of the lot/batch: 2017-01-28
- Purity test date: 2016-02-22

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark
- Stability under test conditions: yes
- Solubility and stability of the test substance in the solvent/vehicle: yes
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no

FORM AS APPLIED IN THE TEST (if different from that of starting material)
- liquid
Species:
other: enucleated chicken eye
Strain:
other: Spring chickens (Gallus Gallus e.g. Ross 308 Broiler)
Details on test animals or tissues and environmental conditions:
Multiple chicken heads (Spring chickens (Gallus Gallus e.g. Ross 308 Broiler)), were supplied by Baileys Turkeys Ltd., Cheshire, UK. The chickens weighed 3kg and were approximately 56 days old prior to being humanely killed for human consumption.
Heads were removed immediately after the chickens had been humanely killed at the source, for use on the same day. The time interval between collection of chicken heads and placing the eyes in the superfusion chamber following enucleation was minimized although all eyes had to fall within the acceptance criteria identified in the test guideline.
Following slaughter, the intact chicken heads were placed into individual plastic compartments within a plastic box in order to minimize any damage to the eyes. The base of each compartment was lined with a paper towel moistened with isotonic saline. The heads were transported to the test facility at ambient temperature.
Vehicle:
unchanged (no vehicle)
Remarks:
For the purpose of this study the test item was used as supplied.
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.03 mL


Duration of treatment / exposure:
The test item remained in place for 10 seconds and was then rinsed from the eye using 20 mL of isotonic saline.
Duration of post- treatment incubation (in vitro):
Treated corneas were evaluated prior to treatment and at 30, 75, 120, 180 and 240 minutes (±5 minutes) after the eyes had been decontaminated with the isotonic saline.
Number of animals or in vitro replicates:
The test item and positive control item groups consisted of three eyes and the negative control item consisted of two eyes.
Details on study design:
SELECTION AND PREPARATION OF ISOLATED EYES
Multiple chicken heads (Spring chickens (Gallus Gallus e.g. Ross 308 Broiler)), were supplied by Baileys Turkeys Ltd., Cheshire, UK. The chickens weighed 3kg and were approximately 56 days old prior to being humanely killed for human consumption.
Heads were removed immediately after the chickens had been humanely killed at the source, for use on the same day. The time interval between collection of chicken heads and placing the eyes in the superfusion chamber following enucleation was minimized although all eyes had to fall within the acceptance criteria identified in the test guideline.
Following slaughter, the intact chicken heads were placed into individual plastic compartments within a plastic box in order to minimize any damage to the eyes. The base of each compartment was lined with a paper towel moistened with isotonic saline. The heads were transported to the test facility at ambient temperature.
Eyes that had a high baseline fluorescein staining (>0.5) or corneal opacity score (>0.5) after the enucleation process were rejected.
The test item and positive control item groups consisted of three eyes and the negative control item consisted of two eyes.
Eyelids were carefully excised whilst taking care not to damage the cornea. The integrity of the cornea was measured with a drop of 2% (w/v) sodium fluorescein to the surface of the cornea and then rinsed with isotonic saline after a few seconds. The treated eyes were examined with the use of the Haag-Streit BQ 900 (Switzerland) microscope, to examine for damage to the cornea. An acceptable eye for the ICE test was one where the fluorescein retention and corneal opacity scores are ≤ 0.5.
Acceptable eyes were dissected from the skull and pulled from the orbit by holding the nictitating membrane firmly with surgical forceps. The tissue behind the eye was carefully removed with bent, blunt-tipped scissors. Once the eye was removed from the orbit a portion of the optic nerve remained. Other connective tissue was removed from the eye on an absorbent tray liner.
Enucleated eyes were transferred to an appropriate clamp keeping the cornea vertical. They were then transferred to chambers within the superfusion apparatus ensuring the corneas received sufficient isotonic saline from the saline drip. The temperature of the chambers was at 32 ±1.5 °C.

EQUILIBRATION AND BASELINE RECORDINGS
Once all eyes were placed in the superfusion apparatus, the eyes were examined again with the Haag-Streit BQ 900 to ensure the eyes had not been damaged by the dissection procedure.
Corneal thickness measurements are taken with a depth measuring device no. 1 on the Haag- Streit BQ 900 slit-lamp microscope at the center of each cornea.
Eyes were replaced when: (i) the fluorescein score was > 0.5; (ii) the corneal opacity score was > 0.5; or (iii) there was any additional signs of damage, (iv) the corneal thickness measurements for individual eyes deviated more than 10% from the mean value for all eyes.
After the approval process the eyes were incubated for 45 minutes for equilibrium purposes.
Time zero measurements for corneal thickness and opacity were taken to serve as a baseline.
The baseline for the fluorescein measurements were taken at dissection.

NUMBER OF REPLICATES
The test item and positive control item groups consisted of three eyes and the negative control item consisted of two eyes.

NEGATIVE CONTROL USED
Identification: Sodium chloride 0.9% w/v
Batch: 3011424
Purity: 0.9%
Physical state / Appearance: clear colorless liquid
Expiry Date: 01 January 2017
Storage Conditions: room temperature

SOLVENT CONTROL USED (if applicable)
Not applicable

POSITIVE CONTROL USED
Information as provided by the supplier.
Identification: Benzalkonium chloride
Batch: A0324149
Purity: unknown
Physical state / Appearance: clear colorless viscous liquid
Expiry Date: 29 July 2016
Storage Conditions: room temperature over silica gel

APPLICATION DOSE AND EXPOSURE TIME
Immediately following the zero reference measurements, each test eye (including clamp) was removed from the superfusion apparatus and placed horizontally (cornea facing upwards) into a petri dish. 0.03 mL of test item was applied to the cornea. The entire surface of the cornea was evenly covered. The test item remained in place for 10 seconds and was then rinsed from the eye using 20 mL of isotonic saline. The treated eye (including clamp) was subsequently returned to the superfusion apparatus in the original upright position.
0.03 mL of the positive control item, Benzalkonium chloride (5%), was similarly applied to the cornea of each positive control eye and 0.03 mL of the negative control item was applied to the cornea of each negative control eye.

OBSERVATION PERIOD
Treated corneas were evaluated prior to treatment and at 30, 75, 120, 180 and 240 minutes (±5 minutes) after the eyes had been decontaminated with the isotonic saline.

REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: The test item remained in place for 10 seconds and was then rinsed from the eye using 20 mL of isotonic saline.
- Indicate any deviation from test procedure in the Guideline: No deviations reported.

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: yes, at 30, 75, 120, 180 and 240 minutes (±5 minutes) after the eyes had been decontaminated with the isotonic saline
- Damage to epithelium based on fluorescein retention: yes, only determined at 30 minutes after test substance exposure
- Swelling: assessed from corneal thickness measurements: yes, at 30, 75, 120, 180 and 240 minutes (±5 minutes) after the eyes had been decontaminated with the isotonic saline
- Macroscopic morphological damage to the surface: yes, at 30, 75, 120, 180 and 240 minutes (±5 minutes) after the eyes had been decontaminated with the isotonic saline

SCORING SYSTEM:
- Mean corneal swelling (%): The overall category score was determined from the highest mean score for epithelial swelling as observed at any time point.
- Mean maximum opacity score: Corneal opacity was calculated with the most densely opacified areas for scoring. The mean value for all test eyes was calculated for all time points. The highest mean score, as observed at any time point was given an overall category for each test item
- Mean fluorescein retention score at 30 minutes post-treatment
-Pitting, sloughing, roughening of the corneal surface, and adhering of test item are all morphological effects that can be noted on the cornea. The classification of these findings was subject to interpretation.

DECISION CRITERIA: please specify if the decision criteria as indicated in the TG was used: yes.
Irritation parameter:
cornea opacity score
Remarks:
Maximal mean score for corneal opacity
Value:
4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
0.5 ICE Class I
Positive controls validity:
valid
Remarks:
4.0: ICE Class IV
Remarks on result:
other: ICE Class IV
Irritation parameter:
fluorescein retention score
Remarks:
Mean score of Fluorescein Retention
Value:
3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
0.5 ICE Class I
Positive controls validity:
valid
Remarks:
3.0 ICE Class IV
Remarks on result:
other: ICE Class IV
Irritation parameter:
percent corneal swelling
Value:
48.57
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
5.19% ICE Class II
Positive controls validity:
valid
Remarks:
39.81% ICE Class IV
Remarks on result:
other: ICE Class IV
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: complete corneal opacity

DEMONSTRATION OF TECHNICAL PROFICIENCY: yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Range of historical values if different from the ones specified in the test guideline: Not applicable
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Following assessment of the data for all endpoints the test item was considered to have the potential to cause ocular corrosivity/severe irritancy in vivo.
Executive summary:

The study was performed to evaluate the possible corrosivity or severe irritancy potential of the test item as measured by its ability to induce toxicity in an enucleated chicken eye.

0.03 mL of the test item was applied onto the cornea of each of three enucleated eyes. A further three enucleated eyes were treated with positive control item. A further two enucleated eyes were treated with negative control item.

Maximal ocular irritation observations recorded for the test item treated eyes were as follows:

Mean Corneal

Opacity

(ICE class)

Mean

Fluorescein

Retention

(ICE class)

% Mean Corneal Thickness

(ICE class)

Combination of the

3 Endpoints

30

mins

75

mins

120 mins

180 mins

240 mins

4.0

(IV)

3.0

(IV)

18.10

31.43

44.76

48.57

46.67

 

(IV)

3 x IV

Classification

Category 1

Mins= Minutes following treatment

Following assessment of the data for all endpoints the test item was considered to have the potential to cause ocular corrosivity/severe irritancy in vivo.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

Phenol 2-(1-methylpropyl) was evaluated for its irritancy potential to the skin of the New Zealand White rabbit. The test material was regarded as corrosive.

Test method:

The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC.

The results may be used as basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced reactions indicative of corrosion. Adverse dermal reactions included haemorrhage of the dermal capillaries, blanching of the skin, scabbing, severe erythema and severe oedema. A single 3 -minute, semi-occluded application of the test material to an additional group of three rabbits produced well-defined to severe erythema and very slight to severe oedema. Other adverse reactions noted were haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, loss of skin elasticity, thickening of the skin, scabbing, reduced re-growth of fur and desquamation.


Effects on skin irritation/corrosion:corrosive

Eye irritation:

The study was performed to evaluate the possible corrosivity or severe irritancy potential of the test item as measured by its ability to induce toxicity in an enucleated chicken eye.

Test method:

0.03 mL of the test item was applied onto the cornea of each of three enucleated eyes. A further three enucleated eyes were treated with positive control item. A further two enucleated eyes were treated with negative control item.

Results:

Maximal ocular irritation observations recorded for the test item treated eyes were as follows:

- Mean Corneal Opacity (ICE class): 4.0 (IV)

- Mean Fluorescein Retention (ICE class): 3.0 (IV)

- Max. % Mean Corneal Thickness (ICE class): 48.57 (IV)

- Combination of the 3 Endpoints: 3 x IV

- Classification: Category 1.

Conclusion:

Following assessment of the data for all endpoints the test item was considered to have the potential to cause ocular corrosivity/severe irritancy in vivo.

Justification for classification or non-classification

Skin irritation / corrosion:

Phenol 2-(1-methylpropyl) is classified according to CLP Regulation (EC) No. 1272/2008 as corrosive to skin and Category 1B classification is proposed with signal word 'Danger' and hazard sentence H314 'Causes severe skin burns and eye damage'.

Eye irritation / corrosion:

Phenol 2-(1-methylpropyl) is classified according to CLP Regulation (EC) No. 1272/2008 as corrosive to eye and Category 1B classification is proposed with signal word 'Danger' and hazard sentence H318 'Causes severe serious eye damage'.