Registration Dossier

Administrative data

Description of key information

The test substance was non-irritating to skin but was found to be irritating to 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:
From 11 Aug, 1993 to 14 Aug, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Three healthy adult rabbits of the New Zealand White strain were obtained from Froxfield (U .K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 2.2 to 2.6 kg
- Housing: Housed individually in metal cages with perforated floors in buliding R 14 room 5
- Diet: Ad libitum, satndard laboratory diet SDS stanrab (P) rabbit diet
- Water: Ad libitum, routine chemical examination of drinking water at source was conducted usually weekly by the supplier
- Acclimation period: Yes

ENVIRONMENTAL CONDITIONS
- Temperature: 19°C
- Humidity: 30 to 70%
- Air changes: 19 changes/h
- Photoperiod: 12 h of artificial light (0700 - 1900 h) in each 24 h period.

Each animal was identified by a numbered aluminium tag placed through the edge of one ear.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL undiluted
Duration of treatment / exposure:
4 h
Observation period:
Observations were made 1, 24, 48 and 72 h after exposure.
Number of animals:
3
Details on study design:
-Treatment: 24 h before treatment, the dorso-lumber region was clipped with electric clippers, exposing an area of approx 100 mm x 100 mm.
- Each animal was treated by dermal application of 0.5 mL of the test substance. The test substance was applied under a 25 mm x 25 mm gauze pad to one intact site on each animal. Each site was covered with elastoplast adhesive dressing for 4 h. The animals were not restrained during the exposure period.
- At the end of exposure the semi-occlusive dressing was removed and the site was washed with warm water to remove any residual test substance and blotted dry with absorbent paper.

-Observation:
Clinical signs: Daily.
Dermal responses: The skin reactions were assessed at approx 1, 24, 48 and 72 h after the removal of the dressings and test substance.The irritation scores and a description of all other (local) effects were recorded.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No effects were observed
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No effects were observed
Irritant / corrosive response data:
No dermal response (erythema or edema) were observed in any animal throughout the observation period
Other effects:
No signs of toxicity or ill health in any rabbit was seen during the observation period.

Results:

Rabbit number and sex

24, 48 and 72 h (erythema and edema scores)

2271-female

0

2272-female

0

2273-female

0

 

Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the test conditions, di-TMPTTA was considered to be non irritating to rabbit skin.
Executive summary:

A study was performed to evaluate the skin irritation potential of di-TMPTTA according to EU Method B.4, in compliance with GLP. Three rabbits were exposed to 0.5 mL of undiluted test substance, applied onto clipped skin for 4 h using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 h after removal of the dressing. Exposure to the test substance did not result in any dermal irritation in the form of erythema or edema. Under the test conditions, the substance was considered to be non-irritating to rabbit skin (Parcell, 1993).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From Aug 24, 1983 to Aug 27, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: Code of Federal Regulation, Title 16, 1500.41
Deviations:
not specified
GLP compliance:
no
Remarks:
Quality assurance audit statement was given.
Species:
rabbit
Strain:
other: White strain
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Pemberley Rabbits, Cottenham, Cambridgeshire
- Age at study initiation: 11-13 weeks
- Weight at study initiation: 2.5-2.8 kg
- Diet : Grain harvester special rabbit diet 474, ad libitum
- Water : Tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19⁰C
- Humidity (%): 30-70%
- Air changes (per hr): 19/h
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light
-IN-LIFE DATES: From Aug 24, 1983 to Aug 27, 1983
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
0.5 mL aliquot
Duration of treatment / exposure:
24 h
Observation period:
24 and 72 h after removal of the patches
Number of animals:
Six
Details on study design:
TEST SITE-
Area of exposure(intact site): Dorso -lumbar region, exposing 10 cm2 of the skin
-Area of exposure(abraded skin): Right side of the spine, exposing 2.5 cm2 of the skin (no bleeding)
- Type of wrap if used: Test substance was applied under a 2.5 cm2 guaze pad to one intact and one abraded skin site on each animal.The treatment site was occluded with "elastoplast" elastic adhesive dressing backed with "sleek" plaster for approximately 24 h.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No (only wiping)
- Time after start of exposure: 24 h

SCORING SYSTEM: Primary dermal irritation index
Irritation parameter:
erythema score
Remarks:
for intact skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 48 h score not measured
Irritation parameter:
erythema score
Remarks:
for intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 48 h score not measured
Irritation parameter:
erythema score
Remarks:
for intact skin
Basis:
animal: 3, 4, 5 and 6
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No adverse effects.
Remarks on result:
other: 48 h score not measured
Irritation parameter:
erythema score
Remarks:
for abraded skin
Basis:
animal: 1, 2, 4, 5 and 6
Time point:
24/48/72 h
Score:
ca. 0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 48 h score not measured
Irritation parameter:
erythema score
Remarks:
for abraded skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 48 h score not measured
Irritation parameter:
edema score
Remarks:
for intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 48 h score not measured
Irritation parameter:
edema score
Remarks:
for intact skin
Basis:
animal: 1, 3, 4, 5 and 6
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No adverse effects
Remarks on result:
other: 48 h score not measured
Irritation parameter:
edema score
Remarks:
for abraded skin
Basis:
animal: 1, 3, 4 and 5
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No adverse effects.
Remarks on result:
other: 48 h score not measured
Irritation parameter:
edema score
Remarks:
for abraded skin
Basis:
animal: 2 and 6
Time point:
24/48/72 h
Score:
ca. 0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 48 h score not measured
Irritant / corrosive response data:
At 24 h, there was a slight erythema with or without oedema in 2 intact and 5 abraded sites, at 72 h, there was a slight erythema with or without oedema in 1 intact site.
Other effects:
No dermal reaction was observed at 24 h or 72 h reading in one animal.
Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the test conditions, the test substance was considered to be mildly-irritating to the rabbit skin, with reversibility within 72 h.
Executive summary:

The skin irritation potential of di-TMPTTA was assessed in a study in rabbit according to the US code of Federal Regulation, Section 1500.41. Six animals were treated for 24 h under an occlusive dressing with 0.5 mL of the test substance applied to one intact and one abraded skin site each. At the end of the exposure period, the occlusive dressing and gauze pads were removed and treatment sites were wiped to remove any residual test substance. The skin was evaluated for erythema, eschar formation and oedema according to the Draize scoring system at 24 and 72 h. At 24 h, there was a slight erythema with or without oedema in 2 intact and 5 abraded sites. At 72 h, there was a slight erythema with or without oedema in 1 intact site. The primary irritation index was calculated by adding the numerical score for erythema and oedema at 24 and 72 h, for both intact and abraded skin and dividing by 24. In this study, the primary irritation index was 0.5. Under the test conditions, the test substance was considered to be mildly irritating to rabbit skin, with reversibility within 72 h (Liggett 1983).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 23, 1992 to June 26, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
other: albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield (UK) Ltd, Peterfield, Hamsphire, England
- Age at study initiation: 11-14 weeks
- Weight at study initiation: 2.3-3.1 kg
- Housing: Individually; metal cages with perforated flooring
- Diet : SDS standrab(P) rabbit diet.ad libitum
- Water:drinking water,ad libitum
-Acclimatization: Yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19⁰C
- Humidity (%): 30-70%
- Air changes (per hr): 19/h
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of the test substance
Duration of treatment / exposure:
4 h
Observation period:
Examination of the treated skin was done on Day 1 (30 mins after removal of dressing) and on Days 2, 3 and 4.
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: 25 mm x 25 mm
- Type of wrap if used: Elastoplast elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with warm water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize system
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: no adverse reaction
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: no adverse reaction
Irritant / corrosive response data:
Non-irritant
Other effects:
All animals were observed daily for signs of ill health and toxicity.
Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the test conditions, di-TMPTTA is considered to be non-irritating to rabbit skin.
Executive summary:

A study was conducted to assess the skin irritation potential of di-TMPTTA to rabbit skin according to EU Method B.4, in compliance with GLP. The shaved skin of three animals was exposed to 0.5 mL of the test substance under semi-occlusive conditions for 4 h. At the end of the treatment period, the semi-occlusive dressing and gauze pads were removed, treatment sites washed with warm water and wiped to remove any residual substance. The skin was evaluated for erythema, eschar formation and oedema according to the Draize scoring system at 30 min, then 24, 48 and 72 h. No dermal reaction was observed. Under the test conditions, the substance was therefore considered to be non-irritating to rabbit skin (Liggett 1992).

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:
From 31 Jan, 1994 to 14 Feb, 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Three healthy adult rabbits of the New Zealand White strain were obtained from Froxfield (U .K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation: 12 to 15 weeks
- Weight at study initiation: 2.8 to 3.4 kg
- Housing: Housed individually in plasticcages with perforated floors in buliding R 14 room 1
- Diet: Ad libitum, satndard laboratory diet SDS stanrab (P) rabbit diet (diet was not analysed for nutrients, contaminants or micro-organisms)
- Water: Ad libitum, routine chemical examination of drinking water at source was conducted usually weekly by the supplier
- Acclimation period: Yes

ENVIRONMENTAL CONDITIONS
- Temperature: 19°C
- Humidity: 30 to 70%
- Air changes (per hr): 19 changes/h
- Photoperiod (hrs dark / hrs light): 12 h of artificial light (0700 - 1900 h) in each 24 h period.

Each animal was identified by a numbered aluminium tag placed through the edge of one ear.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL undiluted
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
Observations were made 1, 24, 48 and 72 h after exposure.
Number of animals or in vitro replicates:
3
Details on study design:
-Treatment: The eyes of each animal was examined prior to instillation of the test substance to ensure that there is no pre-existing corneal damage, iridial or conjunctival inflammation.
- One animal was tested in advance to ensure that if a severe response was produced no further animals would be exposed.

- Single instillation of 0.1 mL undiluted test substance was made in the lower everted lid of one eye of each animal. The lids were then gently held together for about 1 sec to prevent loss of the test substance. The contralateral eye remained untreated.

-Observation:
Clinical signs: Once daily.
Ocular responses: The eyes of each animal were examined approx 1, 24, 48 and 72 h and after 4 and 7 d after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. Observations of the eyes was aided by the use of a handheld light.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 2.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.63
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
Irritation: Instillation of approx 0.1 mL undiluted test substance into one eye of each of three rabbits resulted in corneal opacities, transient iridial inflammation, a diffuse crimson or beefy red coloration of the conjunctivae accompanied by swelling with partial eversion of the eyelids or with the eyelids closed. The eyes became normal 7 d after instillation.
Other effects:
No signs of toxicity or ill health were observed in any rabbit during the observation period.

Results:

Rabbit number

Region of eye

1 h

24 h

48 h

72 h

4 d

7 d

27 (male)

Cornea

dulling

1

1

1

1

0

Iris

0

1

0

0

0

0

Conjunctivae (redness)

2

3

2

1

1

0

Conjunctivae (chemosis)

2

3

2

1

0

0

81 (female)

Cornea

0

1

1

1

1

0

Iris

0

1

1

0

0

0

Conjunctivae (redness)

2

2

3

2

2

0

Conjunctivae (chemosis)

2

2

2

1

1

0

82 (female)

Cornea

0

0

1

1

1

0

Iris

0

0

0

1

0

0

Conjunctivae (redness)

2

2

2

2

2

0

Conjunctivae (chemosis)

2

1

1

1

1

0

Interpretation of results:
other: Category 2 (irritating to eyes) based on CLP criteria
Conclusions:
Under the test conditions, undiluted di-TMPTTA was found to be irritating to the eye of rabbit under CLP (EC 1272/2008) but not under EC (67/548/EEC) criteria.
Executive summary:

A study was performed to assess the eye irritation potential of di-TMPTTA in New Zealand White rabbits according to OECD Guideline 405 and EU Method B.5, in compliance with GLP. 0.1 mL undiluted test substance was placed in the lower everted lid of one eye of each of three animals. The lids were then gently held together for about 1 s to prevent loss of the test substance. The contralateral eye remained untreated and served as a negative control. Instillation resulted in corneal opacities, transient iridial inflammation, and diffuse crimson or beefy red coloration of the conjunctivae accompanied by swelling with partial eversion of the eyelids or with the eyelids closed. The eyes returned to normal 7 d after instillation. Given a conjunctival redness score ≥ 2 but ≤ 2.5 in 2 out of 3 animals, calculated as the mean score following grading at 24, 48 and 72 h and reversible within 21 days, the test substance was considered to be irritating to the eyes of rabbits under CLP (EC 1272/2008) but not under EC (67/548/EEC) criteria (Parcell 1994).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 16 Aug, 1993 to 25 Aug, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Three healthy adult rabbits of the New Zealand White strain were obtained from Froxfield (U .K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation: 12 to 13 weeks
- Weight at study initiation: 2.7 to 3.1 kg
- Housing: Housed individually in metal cages with perforated floors in buliding R 14 room 5
- Diet: Ad libitum, satndard laboratory diet SDS stanrab (P) rabbit diet (diet was not analysed for nutrients, contaminants or micro-organisms)
- Water: Ad libitum, routine chemical examination of drinking water at source was conducted usually weekly by the supplier
- Acclimation period: Yes

ENVIRONMENTAL CONDITIONS
- Temperature: 19°C
- Humidity: 30 to 70%
- Air changes (per hr): 19 changes/h
- Photoperiod (hrs dark / hrs light): 12 h of artificial light (0700 - 1900 h) in each 24 h period.

Each animal was identified by a numbered aluminium tag placed through the edge of one ear.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL undiluted
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
Observations were made 1, 24, 48 and 72 h after exposure.
Number of animals or in vitro replicates:
3
Details on study design:
-Treatment: The eyes of each animal was examined prior to instillation of the test substance to ensure that there is no pre-existing corneal damage, iridial or conjunctival inflammation.
- One animal was tested in advance to ensure that if a severe response was produced no further animals would be exposed.

- Single instillation of 0.1 mL undiluted test substance was made in the lower everted lid of one eye of each animal. The lids were then gently held together for about 1 sec to prevent loss of the test substance. The contralateral eye remained untreated.

-Observation:
Clinical signs: Once daily.
Ocular responses: The eyes of each animal were examined approximately 1, 24, 48 and 72 h and after 4 and 7 d after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. Observations of the eyes was aided by the use of a handheld light.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No adverse effects
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No adverse effects
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: No adverse effects
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
2
Reversibility:
other: No adverse effects
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
2
Reversibility:
other: No adverse effects
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
2
Reversibility:
other: No adverse effects
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
3
Reversibility:
fully reversible within: 3 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
3
Reversibility:
fully reversible within: 3 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
3
Reversibility:
fully reversible within: 3 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 3 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 3 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 3 d
Irritant / corrosive response data:
Irritation: Instillation of 0.1 mL undiluted test substance into one eye of each of three rabbits resulted in dulling of the normal lusture of the cornea after 1 h.
A diffuse crimson coloration of the conjunctivae and swelling with partial eversion of the eyelids or eyelids about half closed was seen in all the three animals.
The eye became normal after 2 or 3 d after instillation.
Other effects:
No signs of toxicity or ill health were observed in any rabbit during the observation period.

Results:

Rabbit number

Region of eye

1 h

24 h

48 h

72 h

4 d

7 d

2296 (male)

Cornea

dulling

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctivae (redness)

2

2

0

0

0

0

Conjunctivae (chemosis)

3

1

0

0

0

0

2297 (female)

Cornea

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctivae (redness)

1

2

1

0

0

0

Conjunctivae (chemosis)

2

2

1

0

0

0

2298 (female)

Cornea

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctivae (redness)

1

1

1

0

0

0

Conjunctivae (chemosis)

2

1

0

0

0

0

Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the test conditions, di-TMPTTA was not irritating to rabbit eye.
Executive summary:

A study evaluated the eye irritation potential of di-TMPTTA in New Zealand White rabbits according to EU Method B.5, in compliance with GLP. In three rabbits, 0.1 mL of the undiluted test substance was placed into the lower everted lid of one eye of each animal and the eyelids were then gently held together for 1 sec before releasing. The contralateral eye remained untreated. Instillation resulted in dulling of the normal lusture of the cornea after 1 h. A diffuse crimson coloration of the conjunctivae and swelling with partial eversion of the eyelids or eyelids about half-closed were seen in all animals. The eyes were normal 2 or 3 d after instillation. Under the test conditions, the substance was considered to be non- irritating to rabbit eye (Parcell 1993).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

A study was conducted to assess the skin irritation potential of the test substance to rabbit skin according to EU Method B.4. The shaved skin of three animals was exposed to 0.5 mL of the test substance under semi-occlusive conditions for 4 h. At the end of the treatment period, the semi-occlusive dressing and gauze pads were removed, treatment sites washed with warm water and wiped to remove any residual substance. The skin was evaluated for erythema, eschar formation and oedema according to the Draize scoring system at 30 min, then 24, 48 and 72 h. No dermal reaction was observed. Under the test conditions, the substance was therefore considered to be non-irritating to rabbit skin(Liggett 1992).

A second study was performed to evaluate the skin irritation potential of the test substance according to EU Method B.4. Three rabbits were exposed to 0.5 mL of undiluted test substance, applied onto clipped skin for 4 h using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 h after removal of the dressing. Exposure to the test substance did not result in dermal irritation in the form of erythema or edema. Under the test conditions, the substance was considered to be non-irritating to rabbit skin(Parcell, 1993).

The skin irritation potential of the test substance was assessed in a final study in rabbit according to the US code of Federal Regulation, Section 1500.41. Six animals were treated for 24 h under an occlusive dressing with 0.5 mL of the test substance applied to one intact and one abraded skin site each. At the end of the exposure period, the occlusive dressing and gauze pads were removed and treatment sites were wiped to remove any residual test substance. The skin was evaluated for erythema, eschar formation and oedema according to the Draize scoring system at 24 and 72 h. At 24 h, there was a slight erythema with or without oedema in 2 intact and 5 abraded sites. At 72 h, there was a slight erythema with or without oedema in 1 intact site. The primary irritation index was calculated by adding the numerical score for erythema and oedema at 24 and 72 h, for both intact and abraded skin, and dividing by 24. In this study, the primary irritation index was 0.5. Under the test conditions, the substance was considered to be mildly irritating to rabbit skin, with reversibility within 72 h(Ligget, 1983).

Eyes

A study was performed to assess the eye irritation potential of the test substance in New Zealand White rabbits according to OECD Guideline 405 and EU Method B.5. 0.1 mL of undiluted test substance was placed in the lower everted lid of one eye of each of three animals. The lids were then gently held together for about 1 sec to prevent loss of the test substance. The contralateral eye remained untreated and served as a negative control. Instillation resulted in corneal opacities, transient iridial inflammation, and diffuse crimson or beefy red coloration of the conjunctivae accompanied by swelling with partial eversion of the eyelids or with the eyelids closed. The eyes returned to normal 7 d after instillation. Given a conjunctival redness score ≥ 2 but ≤ 2.5 in 2 out of 3 animals, calculated as the mean score following grading at 24, 48 and 72 h and reversible within 21 days, the test substance was considered to be irritating to the eyes of rabbits under CLP (EC 1272/2008) criteria(Parcell 1994).

A further study evaluated the eye irritation potential of the test substance in New Zealand White rabbits according to EU Method B.5. In three rabbits, 0.1 mL of the undiluted test substance was placed into the lower everted lid of one eye of each animal and the eyelids were then gently held together for 1 sec before releasing. The contralateral eye remained untreated. Instillation resulted in dulling of the normal lusture of the cornea after 1 h. A diffuse crimson coloration of the conjunctivae and swelling with partial eversion of the eyelids or eyelids about half-closed were seen in all animals. The eyes were normal 2 or 3 d after instillation. Under the test conditions, the test substance was considered to be non-irritating to eyes(Parcell 1993).

Justification for classification or non-classification

The test substance did not show adverse effects on skin in severalin vivoirritation studies. Hence, the substance does not qualify for skin irritation classification according to CLP (EC 1272/2008) criteria.

The test substance was not irritating to eye in one study and moderately irritating in another, whereby individual irritation scores suggest classification Eye Irrit. Cat 2 - H319 (Causes serious eye irritation) according to CLP (EC 1272/2008) criteria.