cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-ylmethyl benzoate

Endpoint summary

Description of key information

Skin irritation:

In a K1 in vivo skin irritation study in New Zealand White rabbits according to OECD Guideline 404 and EU Method B.4, T001095 was observed to be non-irritating to the skin.

Eye irritation:

In a K1 Bovine Corneal Opacity and Permeability (BCOP) test, performed according according to INVITTOX protocol no. 98 "Bovine Corneal Opacity and Permeability Assay" and Bovine Corneal Opacity and Permeability Assay (BCO -P) SOP of Microbiological Associates Ltd., UK, and similar to Draft OECD guideline  437 "The Bovine Corneal Opacity and Permeability (BCOP) Test Method for Identifying Ocular Corrosives and Severe Irritants", T001095 was not considered to be an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-05-24 to 2006-06-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Comparable to OECD Guideline 404 and EU Guildine B.4 study with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

: 1) the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test substance on the skin

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

: 1) the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test substance on the skin

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate from the Swiss GLP Monitoring Authorities

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst / The Netherlands
- Age at study initiation: 12-13 weeks (male); 8-9 weeks (female)
- Weight at study initiation: 2463 g (male); 1726 and 2021 g (females)
- Housing: Housed in a wire cage in compliance with AALAC regulations. Animals were housed ndividually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd., Fullinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 8/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Fullinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: From 2006-05-24 to 2006-05-28 under laboratory conditions after health examination.


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23 deg C, monitored continuously and values outside of the range may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study.
- Humidity (%): air conditioned with relative humidity between 30-70% monitored continuously and values outside of the range may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study.
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hrs light and 12 hrs dark


IN-LIFE DATES: From: 2006-05-24 To: 2006-06-01

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 0.5 mL purified water
- Concentration (if solution): no data


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after exposure

Number of animals:

3 (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: The left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The test substance was applied with a 4 cm x 4 cm surgical gauze patch
- % coverage: no data
- Type of wrap if used: The test substance was applied with a 4 cm x 4 cm surgical gauze patch. The gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours


SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
If evident, corrosive or staining properties of the test substance were described and recorded.

Commission Directive 2004/73/EC, April 29, 2004, Grading of Skin Reactions
Erythema and Eschar Formation:
No erythema =0
Very slight erythema = 1
Well-defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beef redness) or eschar formation (injuries in depth preventing erythema) reading = 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 (edges raised approximately 1 mm) = 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) = 4

Irritation parameter:

erythema score

Basis:

animal: 16

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 16

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal: 17

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicaable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 17

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal: 18

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 18

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test substance did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
Neither alterations of the treated skin were observed, nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining produced by the test substance of the treated skin was observed.
The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), the test substance is considered to be "not irritating" to rabbit skin, and therefore should not be classified.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2006-02-09 to 2006-02-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Well documented non-GLP study performed according to OECD Guideline for testing of Chemicals, Draft OECD Guideline 430, In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER), 27 March 2002.

Qualifier:

according to guideline

Guideline:

other: Draft OECD Guideline 430, In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER), 27 March 2002

Deviations:

no

GLP compliance:

not specified

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00452023 ZT001095PUA121
- Expiration date of the lot/batch:Not indicated by the Sponsor
- Purity test date: Not indicated by the Sponsor

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, protected from moisture
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle: solubility: < 0.05 g/L in water, 37 g/L in acetone, 1.9 g/L in ethanol
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

Test system:

isolated skin discs

Source species:

rat

Source strain:

Wistar

Details on animal used as source of test system:

TEST ANIMALS: epidermal surface of skin discs.
- According to the supplier's assurance the animals were in healthy condition. The animals underwent quarantine in the animal house of RCC - CCR for 6 days after their arrival. During this period the animals did not show signs of illness or altered behaviour.
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Sex: no data
- Age at study initiation (in days): 29 days old
- Weight at study initiation: no data
- Housing: Single, Makrolon Type II, with wire mesh top (EHRET GmbH, D-79302 Emmendingen (EHRET GmbH, D-79302 Emmendingen. Granulated soft wood bedding (Harlan Winkelmann GmbH, D-33178 Borchen) .
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum (Harlan Winkelmann GmbH, D-33178 Borchen)
- Water (e.g. ad libitum): tap water, ad libitum, (Gemeindewerke, D-64380 Rossdorf)
- Acclimation period: minimum of 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 21 +/- 3 deg C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs light, 12 hrs dark

Vehicle:

not specified

Details on test system:

SKIN DISC PREPARATION
- Procedure used: Animals were anaesthetised with CO2 and subsequently decapitated. The dorsal skin of each animal was removed and stripped of excess fat by carefully peeling it away from the skin. The skin was placed over the end of a PTFE (polytetrafluoroethylene) tube, ensuring that the epidermal surface was in contact with the tube. A rubber ‘O’ ring was press-fitted over the end of the tube to hold the skin in place and excess tissue was trimmed away. Tube and ‘O’ ring dimensions are shown in annex 1. The tube was supported by a spring clip inside a receptor chamber containing magnesium sulphate solution (154 mM)

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature

REMOVAL OF TEST MATERIAL AND CONTROLS
- Washing (if done): yes, removed using a jet of warm tap water up to 30 °C until no further material could be removed
-Time after start of exposure: after 24 hour exposure

NUMBER OF INDEPENDENT TESTING RUNS / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if [complete, e.g. if the mean TER value is less than or equal to 5 kΩ and the skin disk is obviously damaged, or if the mean TER value is less than or equal to 5 kΩ, and the skin disc is showing no obvious damage, but the mean disc dye content is greater than or equal to the mean disc dye content of the 10M HCl positive control obtained concurrently.]
- The test substance is considered to be non-corrosive to skin if [complete, e.g. if the mean TER value obtained for the test substance is greater than 5 kΩ, or if the mean TER value is less than or equal to 5 kΩ, and the skin disc is showing no obvious damage, and the mean disc dye content is well below the mean disc dye content of the 10M HCl positive control obtained concurrently.]
- Justification for the selection of the cut-off point(s) if different than recommended in TG 430:

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1686 g, 0.1514 g, or 0.1588 g. 150 uL deionised water was added on top of the test substance and evenly distributed by shaking of the tube.
- Concentration (if solution): not applicable

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 150 µL

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 150 µL
- Concentration (if solution): 36% ~10 M

Duration of treatment / exposure:

24 hours

Number of replicates:

3 skin discs per test group

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Run / experiment:

mean

Value:

15.59

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

Basis: mean. Time point: after 24 hours. Remarks: standard deviation = 6.64.

Other effects / acceptance of results:

The mean electrical resistance (kΩ) was 15.59 +/- 6.64. Following visual inspection, each skin disc was macroscopically intact after treatment.

Table 1.Summary of TER-Results

Sample	Resistance (kOhm)	Mean	Standard Deviation	Corrosive
Negative Control 1	11.36	13.08	4.67	no
Negative Control 2	10.64
Negative Control 3	17.24
Positive Control 1	0.83	0.76	0.07	yes
Positive Control 2	0.75
Positive Control 3	0.69
Test Substance 1	11.87	15.59	6.64	no
Test Substance 2	23.26
Test Substance 3	11.63

 

Interpretation of results:

GHS criteria not met

Conclusions:

It can be stated that the test substance did not corrode rat skin under the experimental conditions used. Both positive and negative control reached typical impedance values as stated in the guideline and in the range of historical controls.

Therefore, the test substance is considered to be non-corrosive in this TER test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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:

2005-10-27 to 2005-10-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Study was conducted according to INVITTOX protocol no. 98 "Bovine Corneal Opacity and Permeability Assay" and Bovine Corneal Opacity and Permeability Assay (BCO-P) SOP of Microbiological Associates Ltd., UK, and similar to Draft OECD guideline 437 "The Bovine Corneal Opacity and Permeability (BCOP) Test Method for Identifying Ocular Corrosives and Severe Irritants". Dec 18, 2008 with the following acceptable deviation: no data was provided on the purity of the test substance.

Qualifier:

according to guideline

Guideline:

other: INVITTOX (UK) protocol no. 98 "The Bovine Corneal Opacity and Permeability Assay", dated February 1994

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Bovine Corneal Opacity and Permeability (BCOP) Assay, SOP of Microbiological Associates Ltd., UK, Procedure Details, April 1997

Deviations:

no

GLP compliance:

not specified

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00452023 ZT001095PUA121
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5 deg C), light protected
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: test substance was tested at a concentration of 20% in saline. Strong stirring with a magnetic stirrer resulted in suspension.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no data

Species:

other: bovine corneas

Strain:

other:

Remarks:

not applicable

Details on test animals or tissues and environmental conditions:

Test system: freshly isolated bovine cornea
Source:. Abattoir Basel, Schlachthofstrasse 55, CH-4055 Basel, Switzerland.
Collection of bovine eyes:
Freshly isolated bovine eyes were collected from the abattoir. After excess tissue was removed from the excised eyes, they were stored at room temperature in Hank's balanced salt solution containing penicillin / streptomycin and then transported for further preparations. The eyes were delivered the day before treatment and the isolated corneas were stored overnight in a preservation medium (Medium 199 supplemented with L-glutamine, Na-biocarbonate and Taurine) in a refrigerator.


Preparation of corneas: All eyes were carefully examined macroscopically for defects. Those presenting defects such as vascularization, pigmentation, opacity, and scratches were discarded. Each cornea was dissected fr om the eye using scalpel and rounded scissors. A rim of about 2-3 mm of tissue (sclera) was left fo r stability and handling of the isolated cornea. All corneas used in the experiment were collected in complete minimum essential medium (cMEM) and were checked finally with a view box for the defect s listed above. Since the bovine eyes were delivered in the afternoon, corneas were stored in a preservation medium over night in a refrigerator at about 4°C. The preservation medium was composed of Medium 199 supplemented with L-glutamine, Na-bicarbonate and Taurine. Shortly before use, dextran was added. Each cornea was mounted in a cornea holder with the endothelial side against the sealing ring (Oring) of the posterior part of the holder. The cornea was gently flattened over the O-ring but stretching had to be avoided. After the anterior part of the holder was positioned on the top of the cornea and fixed in place with screws, both compartments of the holder were filled with cMEM. The posterior compartment had to be filled to return the cornea to its natural convex position. Care must be taken to assure no air bubbles were present within the compartments. For equilibration, the corneas in the holder were incubated for about one hour at 32°C +/- 2°C in a water-bath. At the end of the incubation period, the medium was removed from both compartments and replaced by fresh cMEM, and the basal opacity was determined (t0min). For measurement, the posterior compartment was plugged while the anterior compartment remained unplugged.

Vehicle:

other:

Remarks:

physiological saline natrium chloratum 0.9%

Controls:

other: negative (saline) and positive (imidazole, 20% in saline)

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 20%
Until administration, the solution was stirred with a magnetic stirrer


VEHICLE
- Concentration (if solution): 0.9% sodium chloride in water
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Lot/batch no. (if required): Charge No. 773609
- Purity: no data

NEGATIVE CONTROL - Amount(s) applied (volume or weight with unit): 0.75 mL

POSITIVE CONTROL - Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration (if solution): >/=99.9% (Assay)

Duration of treatment / exposure:

240 minutes

Duration of post- treatment incubation (in vitro):

After 240 ± 1 minutes of treatment, the corneas were thoroughly rinsed to remove test item and incuba ted for 120 ± 10 minutes at 32 ± 1°C with fresh medium followed by opacity measurement. The permeability measurement of the corneas was performed following the opacity measurement after an incubation period of 90 minutes ± 5 minutes.

Number of animals or in vitro replicates:

Three corneas were selected at random for each treatment group

Details on study design:

TREATMENT METHOD:
The medium from the anterior compartment was removed and 750 µL of either the negative control, positive control or test item was introduced onto the epithelium of the cornea. Corneas were incubated for 240 minutes at 32 ± 2°C.

REMOVAL OF TEST SUBSTANCE
Preparation of the test item solution: The test item was tested at a concentration of 20% in saline. Strong stirring with a magnetic stirrer resulted in a solution. Until administration, the solution was stirred with a magnetic stirrer.

REMOVAL OF TEST SUBSTANCE:
- Washing (if done): The test substance was rinsed off from the application side by changing cMEM several times until precipitates of the test substance could be observed no longer, fresh cMEM was replaced inboth compartments and opacity was measured.
- Time after start of exposure: 240 minutes

METHODS FOR MEASURED ENDPOINTS:
- OPACITY MEASUREMENT: After recording the basal opacity of all corneas, the mean value of all corneas was calcualted. No cornea deviated from this by more than +/-3 units and no cornea was discarded. Sets of three cor neas were used for treatment with the test item, the negative and positive controls, respectively. Medium was completely removed from the anterior compartment and replaced by the test item, positiv e or negative control. The anterior compartment was plugged. The holder was turned to a horizontal position and slightly rotated to ensure uniform covering of the cornea with the test item and will be incubated in a horizontal positioning a water-bath at 32°C +/- 2°C.

PERMEABILITY DETERMINATION:
-Following the opacity readings after treatment, the permeability endpoint was measured as an indicated of the integrity of the epithelial cell sheets. After the final opacity measurement was performed, the medium was removed from teh aniterior compartment and repalced by 1 mL of a fluorescein solution. Corneas were incubated again in a horizaontal position for about 90 minutes in a water-bath at 32 ± 2°C. Medium from the posterior compartment was removed with a 5 mL-syringe, well mixed and transferred to a cuvette of 10 mm path length and optical density at 490 nM (OD 490) was determined with a spectophotometer.

In vitro score calculation
The following formula was used to determine the in vitro score: in vitro score = opacity value + (15 x OD490 value)
The in vitro score was calculated for each individual treatment and positive control cornea. The in vitro score value of each treated group was calculated from the individual in vitro score values:
Negative control: in vitro score = opacity value + (15 x OD490 value)
Positive control and test item cornea: in vitro score = corrected opacity value + (15 x corrected OD490 value)
Depending on the score obtained, the test item was classified into one of the following categories:
in vitro score 0 - 3: non eye irritant
in vitro score 3.1 - 25: mild eye irritant
in vitro score 25.1 - 55: moderate eye irritant
in vitro score 55.1 - 80: severe eye irritant
in vitro score > 80.1: very severe eye irritant

Irritation parameter:

in vitro irritation score

Remarks:

mean

Run / experiment:

Test item after 240 minutes of exposure

Value:

0.5

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: SD +/- 0.6

Irritation parameter:

cornea opacity score

Remarks:

mean

Run / experiment:

Test item as 240 minutes of expsure

Value:

0.3

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: SD +/- 0.6

Irritation parameter:

other: permeability value mean

Run / experiment:

Test item after 240 minutes

Value:

0.011

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: SD +/- 0.007

Other effects / acceptance of results:

Other effects / acceptance of results
mean in vitro irritancy score (range):
negative control: 0.5 (-0.7 to 2.2)
positive control: 81.1 (70.5 to 95.1)

mean opacity scores (range):
negative control: 0.3 (-1 to 2)
positive control: 65.7 (59.7 to 71.7)

mean permeability scores (range):
negative control: 0.014 (0.011 to 0.018)
positive control: 1.029 (0.724to 1.561)

Before starting the permeability test, the dye solution sodium fluorescein was checked for its quality. The dye solution is valid for use, if a dilution of the stock solution containing 10 µg/mL showed an optical density (OD490) of 1.610 to 1.910. The value found by spectroscopy was 1.697. According to the results obtained in this experiment, the test was considered acceptable.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the given test conditions, the test substance is not considered to be an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion:

TalviOja (2006) investigated acute dermal irritation of T001095 in New Zealand White rabbits (1 male and 2 females after 4 hours of exposure to 0.5 g of test item). Skin reactions were recorded 1, 24, 48 and 72 hours after administration and scored according to the Draize scale. No evidence of skin irritation was noted. The test item did not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.

In addition, Meurer (2006) investigated the dermal corrosion of T001095 in isolated skin discs from the Wistar rat (3 skin discs after 24 hours of exposure to 0.1686 g, 0.1514 g, or 0.1588 g of test item). The transcutaneous electrical resistance was measured. The test item did not corrode the rat skin, therefore, the test item did meet the criteria for classification as corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.

Eye irritation:

Deparade (2006) investigated eye irritation in an in vitro bovine corneal opacity-permeability (BCOP) assay. 750 μl of T001095 (20% w/v suspension in physiological saline) was applied for 240 minutes. Both opacity and permeability were measured and the resulting objective values were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS). A mean in vitro irritancy score of 0.5 SD +/- 0.6 was calculated after 240 minutes of treatment. Since the test item induced an IVIS ≤3 , it is concluded that T001095 is a not an eye irritant in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in the report and should not be classified as an eye irritant according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations.

Justification for classification or non-classification

Skin irritation:

According to the in vivo acute dermal irritation study no evidence for skin irritation was noted for T001095. The test item did not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.

Eye irritation:

According to the in vitro eye irritation study (BCOP) no evidence for eye irritation was noted for T001095. The test item did not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.