Registration Dossier

Administrative data

Description of key information

Di-TMP was found to be non-irritating to skin and was a mild eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 June 1995 - 30 June 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed to GLP and according to appropriate OECD and EC test guidelines
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
Species:
rabbit
Strain:
other: SPF albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mol:Russian stock from Møllegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved
- Weight at study initiation: 2.1 - 2.5 kg.
- Housing: Animals caged individually in PPO/HIPS (Noryl) cages (floor area 2576 cm2) with perforated floor.
- Diet (e.g. ad libitum): Ad libitum access to pelleted complete rabbit diet "Altromin 2123" from Chr. Petersen, DK-4100 Ringsted.
- Water (e.g. ad libitum): Ad libitum access to domestic quality drinking water, acidified to pH 2.5 with hydrochloric acid to prevent microbial growth.
- Acclimation period: At least one week.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3ºC
- Humidity (%): 55±15%
- Air changes (per hr): 10 air changes/hour.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours darkness.


IN-LIFE DATES: From: 19 June 1995 To: 30 June 1995
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g solid test material moistened using 0.5 mL distilled water was applied to 2.5 x 2.5 cm patches.
Duration of treatment / exposure:
4 hours.
Observation period:
Observations made 1 hour after removal of dressing / test material then 24, 48, and 72 hours after termination of exposure.
Number of animals:
3 female rabbits.
Details on study design:
TEST SITE
- Area of exposure: 2 patches, 2.5 x 2.5 cm on each animal.
- Type of wrap if used: gauze patches secured with a semi-occlusive dressing by means of a 1cm wide adhesive tape and fixed with Scanpor tape,
4.5 cm width, loosely wound round the trunk.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Patches removed and the skin was washed with lukewarm water
- Time after start of exposure: 4 hours


SCORING SYSTEM: Scoring system used was consistent with system described in OECD test guideline 404.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation were observed during the observation period.
Other effects:
None

Rabbit No.

Weight kg

Test field

Erythema-Eschar observed at hours*

Individual mean values

Oedema observed at hours*

Individual mean values

1

24

48

72

1

24

48

72

7697

2.5

L

0

0

0

0

0.00

0

0

0

0

0.00

R

0

0

0

0

0

0

0

0

7700

2.1

L

0

0

0

0

0.00

0

0

0

0

0.00

R

0

0

0

0

0

0

0

0

7703

2.2

L

0

0

0

0

0.00

0

0

0

0

0.00

R

0

0

0

0

0

0

0

0

Mean of rabbits

 

 

 

 

 

0.0

 

 

 

 

0.0

Only the scores from the 3 readings (24, 48, and 72 hours) are included in the calculation of the individual mean values.

* after termination of exposure

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
DiTMP was found ot be non-irritating to skin, under the conditions of this study and does not require classfication as a skin irritant according to the CLP Regulation.
Executive summary:

An acute skin irritation study was performed to determine the potential for skin irritation of Di-TMP. The study was conducted to GLP and according to OECD 404 and EC B4 Test Guidelines. No signs of irritation were observed following exposure to the test substance. Di-TMP is not classified as irritating according to CLP.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 June 1995 - 30 June 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed to GLP and according to appropriate OECD and EC Test Guidelines
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
Species:
rabbit
Strain:
other: SPF albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Mølle-gaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved.
- Weight at study initiation: 2.4 kg
- Housing: Animals housed individually in PPO/HIPS (Noryl) cages (floor area: 2576 cm2) with perforated floor.
- Diet (e.g. ad libitum): Pelleted complete rabbit diet "Altromin 2123" from Chr. Petersen, DK-4100 Ringsted. Available ad libitum.
- Water (e.g. ad libitum): Free access to bottles containing domestic quality drinking water acidified with hrdyochloric acid to pH 2.5
- Acclimation period: At least one week.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3ºC.
- Humidity (%): 55±15%.
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light):12 hours light / 12 hours darkness.


IN-LIFE DATES: From: 25 June 1995 To: 30 June 1995
Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye in each animal was treated with test material; the right eye was untreated and used as the control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g
Duration of treatment / exposure:
Eye lids held shut for 1 second following instillation of the test material into the eye. Exposure was otherwise instantaneous.
Observation period (in vivo):
Eyes were observed after 1, 24, 48, and 72 hours from exposure. After the initial 24 hour assessment, Fluorescein was instilled, the eyes rinsed with saline solution and the eyes examined again using UV light.
Number of animals or in vitro replicates:
3 female rabbbits.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes rinsed following Fluorescein instillation (24 hours) but no dedicated rinsing performed following test substance exposure.


SCORING SYSTEM: Scoring of irritation was largely consistent with the scheme detailed in OECD test guideline 405. Evaluation of scores was based on The Official Journal of the European Communities, L110A, 1993, teh directive of teh comission 93/21/EEC of April 27, 1993.


TOOL USED TO ASSESS SCORE: Fluorescein used, as detailled previously. Also used was a hand held inspection lamp fitted with white and UV-light and magnifying glass with 2x magnification.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Moderate conjuntival irritation (chemosis, redness, discharge) was observed in all rabbits 1 to 48 hours after exposure. Slight corneal opacity was
seen in all rabbits 1 to 24 hours after exposure and in two rabbits 48 hours after exposure. At 72 hours no abnormalities were observed.

Scores for ocular lesions

Rabbit No. / Weight kg

Effect and severity

1 hr

24 hrs, F

48 hrs, F

72 hrs, F

Individual mean score

7695 / 2.4

Corna opacity, area

1

2, 2

1, 1

0, 0

 

Cornea opacity, degree

1

1

0

0

0.33

Iris

0

1

0

0

0.33

Conjunctiva chemosis

2

2

0

0

0.67

Conjunctiva redness

2

2

2

0

1.33

Conjunctiva discharge

3

0

0

0

 

76977/ 2.4

Corna opacity, area

4

1, 1

1, 1

0, 0

 

Cornea opacity, degree

1

1

1

0

0.67

Iris

0

1

0

0

0.33

Conjunctiva chemosis

3

3

1

0

1.33

Conjunctiva redness

1

2

2

0

1.33

Conjunctiva discharge

2

0

0

0

 

7680 / 2.4

Corna opacity, area

4

1, 1

1, 1

0, 0

 

Cornea opacity, degree

1

1

1

0

0.67

Iris

0

1

0

0

0.33

Conjunctiva chemosis

4

3

1

0

1.33

Conjunctiva redness

2

2

1

0

1.00

Conjunctiva discharge

2

0

0

0

 

 

F: reading after instillation of oculoguttae fluoresceini

Only the scores from the 3 readings (24, 48, and 72 hours) are included in the calculation of the individual mean scores.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, Di-TMP was found to be a moderate eye irritant but does not require classification as an eye irritant according to the CLP Regulation.
Executive summary:

An eye irritation study was performed to determine the potential for irritation to eyes when 0.1g of the test substance Di-TMP was administered to the left eye of three rabbits. The study was conducted to GLP and according to OECD 405 and EC B5 Test Guidelines. Moderate conjunctival irritation (chemosis, redness, discharge) was observed in all rabbits 1 to 48 hours after exposure. Slight corneal opacity was seen in all rabbits 1 to 24 hours after exposure and in two rabbits 48 hours after exposure. At 72 hours no abnormalities were observed. Under the conditions of this study, Di-TMP was found to be a moderate eye irritant but does not require classification as an eye irritant according to the CLP Regulation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No evidence of skin irritation was seen with di-TMP (Aarup, 1995). The substance was found to be a mild eye irritant, with all effects reversible within 72 hours (Aarup, 1995).


Justification for selection of skin irritation / corrosion endpoint:
Single study available for this endpoint

Justification for selection of eye irritation endpoint:
Single study available for this endpoint

Justification for classification or non-classification

The results of the available skin and eye irritation studies do not trigger classification of Di-Trimethylolpropane as skin or eye irritant according to Regulation (EC) No 1272/2008.