Registration Dossier

Administrative data

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 (Esposito, 2007), no evidence for skin irritation was noted for T002675.


Eye irritation:

In a K1 in vivo eye irritation study in New Zealand White rabbits according to OECD Guideline 405 and EU Method B.5 (Arcelin, 2007), T002675 was observed not to be irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-03-14 to 2007-03-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study performed according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and EU Method B.4 (Acute Toxicity: Dermal Irritation) without deviation.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate issued by the Swiss GLP Monitoring Authorities
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 603T-1
- Expiration date of the lot/batch: 2007-12-19
- Purity test date: no data
- Purity: 97.76%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 ± 5 °C, provided by RCC), light protected.
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Test item was applied undiluted as it was delivered by the sponsor.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: 3 male and 3 female young adult New Zealand White Rabbit, SPF; Harland Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst, The Netherlands/Postbus 6174, NL-5960 AD Horst, The Netherlands
- Age at study initiation: 12-13 weeks for males; 11-13 weeks for females
- Weight at study initiation: 2150-2386 g
- Housing: standard laboratory conditions; individually in stainless steel cages with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 batch 08/07 were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch 83/06 and 01/07), ad libitum
- Water (e.g. ad libitum): Füllinsdorf community tap water, ad libitum
- Acclimation period: 4 days, under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): approximately 10-15
- Photoperiod (hrs dark / hrs light): 12/12, automatically controlled light cycle. Music was played during the daytime light period.

IN-LIFE DATES: From: 2007-03-19 To: 2007-03-22
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): test matreial was applied undiluted
Duration of treatment / exposure:
4 hours
Observation period:
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test substance).
Number of animals:
3 (1 ale and 2 females)
Details on study design:
TEST SITE
- Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
- Area of exposure: left flank (ca. 2.5 cm x 2.5 cm)
- % coverage: no data
- Type of wrap if used: the test item was placed on a surgical gauze patch. This 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): The dressing was removed and the skin was flushed with lukewarm tap water.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- Viability/Mortality: daily from acclimatization of the animals to the termination of test.
- Clinical signs: daily from acclimatization of the animals to the termination of test.
- Body weights: at start of acclimatization, on the day of application and at termination of observation.
- Skin reactions: approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item)

SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
- The three animals showed very slight erythema at 1 hour which did not persist. The mean score was calculated across three scoring times (24, 48, and 72 hours) for erythema and edema grades, separately. The two mean scores were 0 for all animals. No abnormal findings were observed on the treated skin 24 hours after treatment.
Other effects:
VIABILITY/MORTALITY
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

COLORATION
- No staining by the test item of the treated skin was observed.

CORROSION
- Neither alterations of the treated skin was obsrved nor were corrosive effects evident on the skin.

BODY WEIGHTS
-The body weights of all animals 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), TIC876 (T002675) is considered to be “not irritating” to rabbit skin.
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-03-28 to 2007-04-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study performed according to OECD Guideline 405 (Acute Eye Irritation / Corr and EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion) without deviation.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Remarks:
Certificate issued by the Swiss GLP monitoring authorities
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 603T-1
- Expiration date of the lot/batch: 2007-12-19
- Purity test date: no data
- Purity: 97.76%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test item was applied undiluted as it was delivered by the sponsor
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: 3 male and 3 female young adult New Zealand White Rabbits; Harland Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst, The Netherlands; Postbus 6174, NL-5960 AD Horst, The Netherlands
- Age at study initiation: 11-12 weeks for males; 11-13 weeks for females
- Weight at study initiation: 2082-2271 g
- Housing: standard laboratory conditions; individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 batch no.08/07 were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch 01/07), ad libitum
- Water (e.g. ad libitum): Füllinsdorf community tap water, ad libitum
- Acclimation period: 5 days, under laboratory conditions after health examination. Only animals without any visual signs of illnes were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): approximately 10-15
- Photoperiod (hrs dark / hrs light): 12/12, automatically controlled light cycle. Music was played during the daytime light period.

IN-LIFE DATES: From: 2007-04-02 To: no data
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): test item was applied undiluted

Duration of treatment / exposure:
single application
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48, 72 hours, as well as 7 days after administration.
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not performed

SCORING SYSTEM:
- The eye reactions were assessed according to the numerical scoring system listed in the Commission Directive 2004/731EC, April 29, 2004. Scleral reddening and ocular discharge were also assessed.

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
conjunctivae score
Remarks:
: redness
Basis:
animal #4
Remarks:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
: redness
Basis:
animal #5
Remarks:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
: redness
Basis:
animal #6
Remarks:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: same score- all 3 animals
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: same score- all 3 animals
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable - score 0
Irritant / corrosive response data:
- No abnormal findings in the cornea or iris of any animal at any time.
- A slight to moderate reddening of the conjunctivae was noted in all animals 1 hour after instillation, and persisted up to 48 hours in the male and 72 hour in the females.
- Slight to moderate swelling of the conjunctivae was noted at the 1 hour observation that persisted to 24 hours.
- All animals had slight to moderate reddening of the sclera, 1-48 hours in the male, to 72 hours in the females, and slight to moderate discharge was present 1 to 24 hours after instillation in all animals.
- No abnormal findings were observed in the treated eye of any animal 7 days after treatment, the end of the observation period for all animals.
Other effects:
VIABILITY/MORTALITY
- No clinical signs of systemic toxicity were observed, and no mortality occurred during the study.

COLORATION
- No staining of the treated eyes by the test item was observed.

CORROSION
- No corrosion of the cornea was noted at any of the observation times.

BODY WEIGHTS
- The body weights of all rabbits were considered to be within the normal range of variability.

Eye Irritation Scores - Individual Values

Animal Number

Sex

Evaluation Interval

Corneal Opacity

Area of Corneal Opacity

Iris

Conjunctivae

Sclera

Redness

Chemosis

4

M

1 hour

0

0

0

1

2

1

5

F

0

0

0

1

2

1

6

F

0

0

0

1

2

2

4

M

24 hours

0

0

0

1

1

1

5

F

0

0

0

2

1

2

6

F

0

0

0

1

1

2

4

M

48 hours

0

0

0

1

0

1

5

F

0

0

0

1

0

1

6

F

0

0

0

1

0

1

4

M

72 hours

0

0

0

0

0

0

5

F

0

0

0

1

0

1

6

F

0

0

0

1

0

1

4

M

7 days

0

0

0

0

0

0

5

F

0

0

0

0

0

0

6

F

0

0

0

0

0

0

* Examinations were performed at the specified times after instillation of the test item.

 

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the reffered classification(Commission Directive 2001/59/EC of August 06, 2001), T002675 is considered to be "not irritating" to the rabbit eye.
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

Esposito (2007) investigated skin irritation potential of T002675 in New Zealand White rabbits (1 male, 2 females after for hours of exposure to 0.5 mL of the test item). Each test site was examined and scored separately for erythema and edema on a graded scale of 0 to 4 (primary dermal irritation index). The mean score was calculated across 3 scoring times (24, 48, and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

The three animals showed very slight erythema at 1 hour which did not persist (full reversibility of effects). No abnormal findings were observed on the treated skin 24 hours after treatment. 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.

  

An in vitro skin irritation study was waived based on the justification that adequate data from an in vivo

skin irritation study are available.

 

Eye irritation:

Arcelin (2007) investigated eye irritation potential in an in vivo eye irritation study.

0.1 mL of T002675 (undiluted) was applied to the left eye of 3 New Zealand White rabbits (one male and two females). The treated eyes were not rinsed after instillation.
The ocular reaction was assessed at approximately 1, 24, 48 and 72 h, as well as 7 days after administration for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all the three animals. The individual mean scores for the conjunctivae were 0.67, 1.33 and 1.00 for reddening and 0.33 for chemosis for each of the three animals.

The instillation of T002675 into the eye resulted in mild to moderate, early onset and transient ocular changes, such as slight to moderate reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. 


T002675 is considered to be not irritating to the rabbit eye.

An in vitro eye irritation study was waived based on the justification that adequate data from an in vivo

eye irritation study are available.


Justification for classification or non-classification

Skin irritation:

According to the in vivo skin irritation study no evidence for skin irritation was noted for T002675. 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 vivo eye irritation study, T002675 was observed not to be irritating to eyes. The test item did not meet the criteria for classification for eye irritation or serious eye damage according to the criteria of the CLP Regulation (EC) No 1272/2008.