Registration Dossier

Administrative data

Description of key information

Skin Irritation

Severe erythema, moderate to severe edema, necrosis on 6 of 6 rabbits from 0.5 ml; ulceration, scabs also apparent; irritation Dersisted through 14 days. Corrosive to skin.

Eye Irritations

Persistent, minor, diffuse corneal opacity in 6 of 6 eyes, iritis in 6, moderate to severe conjunctival irritation in 6 from 0.005 ml; conjunctival necrosis, instances of corneal vascularization observed; 3 healed, 3 still injured at 21 days.

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:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
New Zealand White rabbits, weighing between 2.0 and 3.0 kg,
The animals are maintained on appropriate commercial diet and municipal water. Both are available ad libitum expect during periods of manipulation. Animal weights are recorded at 0 days (before dose), 7 days and 14 days (just prior sacrifice). At death or sacrifice, each animal is subjected to gross pathological evaluation.
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5ml
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
6
Details on study design:
Male or female New Zealand White rabbits are dosed with 0.5 ml (or 0.5 g for solids, moistened with water or other suitable vehicle). The dose is applied to the clipped, intact skin under a gauze patch and is loosely covered with impervious sheeting. Smaller amounts are given if 0.5 ml (or 0.5 g) is lethal. The test material is applied to each of 6 rabbits, which are restrained for the 4-hr contact period.

Excess sample is removed after contact. Skin reaction is scored, by the method of Draize, at one hour, one day, 2 days, 3 days, 7 days, and, depending on the local skin reaction, possibly 10 and 14 days after dosing.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
3.2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
mean
Time point:
14 d
Score:
0.3
Max. score:
1
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
3.3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
3
Max. score:
3
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
2.7
Max. score:
3
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
21 d
Score:
1.2
Max. score:
2
Reversibility:
not specified
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
Skin Irritation, Rabbit (4-hr occluded)
Severe erythema, moderate to severe edema, necrosis on 6 of 6 rabbits from 0.5 ml; ulceration, scabs also apparent; irritation persisted through 14 days. Corrosive to skin.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Male or female Hew Zealand White rabbits
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
Male or female New Zealand White rabbits are dosed with volumes of 0.1, 0.01 and 0.005 ml (liquid or solid).
Duration of treatment / exposure:
One application
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
6 animals
Details on study design:
Male or female New Zealand White rabbits are dosed with volumes of 0.1, 0.01 and 0.005 ml (liquid or solid). The dose is instilled into the lower conjunctival sac of one eye per animal or is placed directly on the eye. The eyelids are held together for one second. Six eyes are dosed per test volume. The eyes are scored by the attached system at one hour, approximately 4 hours, one day, 2 days, 3 days and 7 days after dosing. Additional readings are made, if necessary, at 14 and 21 days. Fluorescein (2%) staining is used to determine corneal injury before dosing and at readings after one day.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
0.8
Max. score:
1
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
14 d
Score:
1.3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
21 d
Score:
1
Max. score:
3
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
3
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
7 d
Score:
1.2
Max. score:
2
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
14 d
Score:
0.5
Max. score:
1
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
21 d
Score:
0.5
Max. score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
14 d
Score:
0.3
Max. score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
21 d
Score:
0.2
Max. score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0.5
Max. score:
1
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
7 d
Score:
1.5
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
14 d
Score:
0.7
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
21 d
Score:
0.8
Max. score:
2
Reversibility:
not specified
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Persistent, minor, diffuse corneal opacity in 6 of 6 eyes, iritis in 6, moderate to severe conjunctival irritation in 6 from 0.005 ml; conjunctival necrosis, instances of corneal vascularization observed; 3 healed, 3 still injured at 21 days.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

Skin Irritation:

Category 1 (skin corrosion) =

Destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least one tested animal after exposure equal to 4 h

Note: This category is further subdivided in three sub-categories (1A, 1B, 1C). Corrosive substances shall be classified in Category 1 where data is not sufficient for sub-categorisation. When data are sufficient, substances shall be classified in one of the three sub-categories 1A, 1B, or 1C.

6 of 6 animals demonstrated scores of 4 at 4 hours. The study report does not include information on irritation at under 4 hours therefore sub catagorisation cannot be applied.bTherefore DDPA is considered a Category 1 skin irritant.

Eye Irritation:

Category 2 =

Substances that produce in at least in 2 of 3 tested animals, a positive response of:

(a) corneal opacity = 1 and/or

(b) iritis = 1, and/or

(c) conjunctival redness = 2 and/or

(d) conjunctival oedema (chemosis) = 2

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days

6 out of 6 animals demonstrated a score of 1 (corneal opacity) at 24, 48 and 72 hours. Therefore DDPA is considered a Category 2 eye irritant.