Registration Dossier

Administrative data

Description of key information

No signs of skin irritation in a GLP study conducted according to OECD guideline 404 (null scores for erythema and edema in all animals) were observed. Only slight signs of eye irritation were observed in a GLP study conducted according to OECD guideline 405.
So, in conclusion, TMPTMA is considered to be not skin or eye irritating.

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:
From July 05 to 08, 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
systemic effects not followed; animals not weighed at the end of the study
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, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.0-3.5 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): Certified Rabbit Diet (Code 5322) (BCM IPS Limited, London, UK), ad libitum
- Water (e.g. ad libitum): Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours 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 with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
Three males
Details on study design:
TEST SITE
- Area of exposure: Dorsal flank area
- Type of wrap if used: Test material (0.5 mL) was applied beneath a gauze (2.5 cm X 2.5 cm), placed directly on the test sites and then secured in position with surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
- Very slight erythema was observed at the application sites which subsided within 24 hours
- See table 1 for individual animal scores
Other effects:
No

Table 1: Individual skin reactions

Rabbits No.

62 Male

63 Male

64 Male

Erythema/Eschar

1 hour

1

1

1

24 hours

0

0

0

48 hours

0

0

0

72 hours

0

0

0

Mean (24 hours + 48 hours + 72 hours)

0

0

0

Oedema

1 hour

0

0

0

24 hours

0

0

0

48 hours

0

0

0

72 hours

0

0

0

Mean (24 hours + 48 hours + 72 hours)

0

0

0

Interpretation of results:
GHS criteria not met
Remarks:
not skin irritating
Conclusions:
Under the test conditions, TMPTMA is not classified as irritating to the skin according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In a primary dermal irritation GLP study performed according to OECD guideline 404, three New-Zealand white male rabbits were dermally exposed to 0.5 mL of TMPTMA, under a semi-occlusive bandage (25 cm X 25 cm) for 4 hours to clipped skin of dorsal flank area. Animals then were observed for 72 hours. Irritation was scored by the method of Draize (1959).

Very slight erythema was observed at the application sites which subsided within 24 hours. Mean individual scores at 24, 48 and 72 hours after removal of the test material for the 3 animals were 0, 0, 0 for erythema/oedema score. In this study, TMPTMA is not a dermal irritant on male rabbits.

Under the test conditions, TMPTMA is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

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:
From July 11 to 21, 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no data on non-ocular local and systemic adverse effects
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.0-3.5 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): Certified Rabbit Diet (Code 5322) (BCM IPS Limited, London, UK), ad libitum
- Water (e.g. ad libitum): Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume with unit): 0.1 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Three males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: Not applicable

SCORING SYSTEM: Draize (1977) scoring system

TOOL USED TO ASSESS SCORE: Eye examinations were performed using light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
- Minimal conjunctival irritation was noted in all treated eyes 1 and 24 hours after treatment and in one treated eye at the 48 hour observation; irritation completely resolved within 72 hours
- See table 1 and 2 for further details
Other effects:
No data

Table 1: Individual eye irritation scores

Animal

Time after dosing (hours)

Cornea

Iris

Conjunctivae

Opacity

Area

Redness

Chemosis

Discharge

126 Male

1

0

0

0

1

0

1

24

0

0

0

1

0

0

48

0

0

0

1

0

0

72

0

0

0

0

0

0

30 Male

1

0

0

0

1

1

1

24

0

0

0

1

0

0

48

0

0

0

0

0

0

72

0

0

0

0

0

0

31 Male

1

0

0

0

1

1

1

24

0

0

0

1

0

0

48

0

0

0

0

0

0

72

0

0

0

0

0

0

Table 2: Mean (24, 48 and 72 hours) value eye irritation scores

Animal

Corneal opacity

Iris

Conjunctivae

Redness

Chemosis

126 Male

0

0

0.7

0

30 Male

0

0

0.3

0

31 Male

0

0

0.3

0

Interpretation of results:
GHS criteria not met
Remarks:
not eye irritating
Conclusions:
Under the test conditions, TMPTMA is not classified as irritating to the eye according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted TMPTMA in their right eye (under local anaesthesia) while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 1, 24, 48 and 72 hours after dosing and graded according to the method of Draize (1977).

 

Minimal conjunctival irritation was noted in all treated eyes 1 and 24 hours after treatment and in one treated eye at the 48 hour observation. The irritation completely resolved within 72 hours. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.3, 0.3 for conjunctivae score and 0, 0, 0 for chemosis score.

 

Under the test conditions, TMPTMA is not classified as irritating to the eye according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A recent GLP study (2005) conducted according to OECD guideline 404, using TMPTMA, showed that mean individual scores at 24, 48 and 72 h after removal of the test material for 3 rabbits were 0, 0, 0 for erythema/oedema score. This study was chosen as key study because it was the most recent study and because other studies had less details about test substance and animal housing conditions. Another study performed in similar conditions confirmed this result. A study conducted in drastic conditions (24 h exposure in occusive conditions) showed only slight signs of skin irritation.

In a primary dermal irritation GLP study (1996) performed according to OECD guideline 404, three New-Zealand white rabbits were dermally exposed to 0.5 mL of TMPTMA, under a semi-occlusive conditions for 4 hours to clipped skin of dorsal flank area. Animals were then observed for 72 hours. Irritation was scored by the method of Draize (1959). Very slight erythema was observed at the application sites which subsided within 24 hours. Mean individual scores at 24, 48 and 72 hours after removal of the test material for the 3 animals were 0, 0, 0 for erythema/oedema score. In this study, TMPTMA is not a dermal irritant in rabbits.

Eye irritation

A recent GLP study (2005) conducted according to OECD guideline 405, using TMPTMA, showed that mean individual scores at 24, 48 and 72 h after exposure of 3 rabbits were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.3, 0.3 for conjunctivae score and 0, 0, 0 for chemosis score. This study was chosen as key study because it was the most recent study and because other studies and less details about test substance and animal housing conditions.

In another GLP eye irritation study (1999) conducted similarly to OECD guideline 405, no signs of irritation were observed in 6 rabbits.

Justification for classification or non-classification

In studies conducted according to OECD guidelines, no signs of eye and skin irritation that could lead to classification were observed. Therefore, TMPTMA is not classified according to the CLP Regulation (EC) N° (1272-2008).