Registration Dossier

Administrative data

Description of key information

The key studies for skin and eye irritation found the test substance not irritating (Safepharm Laboratories 1982, rel 1).

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:
27.07.1982 to 30.07.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, UK and Hylyne Rabbits Ltd, Cheshire, UK.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.75 to 2.96 kg
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): Not controlled (76-80)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 27.07.1982 to 30.07.1982
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
Seven days
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: Back
- % coverage: No data
- Type of wrap if used: Elasticated corset


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: Four hours


SCORING SYSTEM: Draize
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:
Slight erythema in one animal after one hour. No other signs of irritation.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline skin irritation study conducted to GLP (reliability score 1) sodium salt of ATMP was not irritating to the skin of rabbits following a four hour exposure.
Executive summary:

In a guideline skin irritation study conducted to GLP (reliability score 1) sodium salt of ATMP was not irritating to the skin of rabbits following a four hour exposure.

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:
24.08.1982 to 27.08.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hylyne Rabbits Ltd., Cheshire, UK.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.12 to 2.33 kg
- Housing: Individually housed in suspended metal cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 ±2.5
- Humidity (%): 68-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 24.08.1982 to 27.08.1982
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Amount applied: 0.1 ml
Duration of treatment / exposure:
Eyes not rinsed.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Three
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis 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:
Mild conjunctival inflammation, with or without slight swelling was observed in all three animals after one hour. A dulling of the normal lustre of the cornea was observed in two rabbits at the one hour reading. In one animal this was accompanied by iritis. The reactions had ameliorated in two rabbits by 24 hours when mild conjunctival inflammation only was seen in the remaining animal. This reaction persisted until the 72 hour observation point.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline eye irritation study conducted to GLP (reliability score 1) the sodium salt of ATMP was not irritating to the eyes of rabbits.
Executive summary:

In a guideline eye irritation study conducted to GLP (reliability score 1) the sodium salt of ATMP was not irritating to the eyes of rabbits.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key studies were selected based on their high reliability and recency. The supporting studies were in accordance with the key information.

Justification for classification or non-classification

The tested ATMP salts do not exhibit extreme pH (=<2 or =>11.5), therefore local effects on the skin and eye due primarily to high or low pH would not be anticipated. Reliable studies on several different formulations consistently demonstrate a low degree of irritation, well below the threshold for classification.

No data are available on lower or higher pH salts with x=2 or x=6. For these it is more appropriate to base classification on that proposed for ATMP acid.

It is concluded that classification for eye irritation or corrosion is not required for ATMP salts with x=3-5.

For ATMP salts where x=2 or x=6, classification for eye irritation in Category 2 (H319) may be appropriate.

Since ATMP acid does not exhibit skin irritation or corrosion leading to classification, these salts would also be expected to exhibit only mild irritant effects on the skin.It is concluded that classification for skin irritation or corrosion is not required for ATMP salts.