Registration Dossier

Administrative data

Description of key information

Skin irritation: corrosive (acute dermal toxicity study EPA 40 CFR, Par. 158.50 & 158.135, Subdivision F, Section 81-2; 40 CFR, Subdivision F, par. 158.50 and 158.135; Section 81-5)

 

Eye irritation: irreversible damage to the eye (EPA OPP 81-4)

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: 40 CFR, Subdivision F, par. 158.50 and 158.135; Section 81-5, pg. 55-59, Primary Dermal Irritation
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: at least 2-3 kg
- Diet (e.g. ad libitum): rabbit diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 65-75°F
- Humidity (%): 40-60%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped; intact + abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL


Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
6
Details on study design:
OBSERVATION TIME POINTS
1, 24, 48, and 72 hours after patch removal

SCORING SYSTEM:
Draize scale
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal: 1-6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal: 1, 3, 4, 5, 6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
All animals displayed severe blistering and eschar formation.

Score at time point

Erythema, intact skin

Erythema, abraded skin

Edema, intact skin

Edema, abraded skin

Max. score: 4

Max. score: 4

Max. score: 4

Max. score: 4

60 min

2/2/2/2/1/2

3/3/3/3/3/3

2/3/2/3/2/2

3/4/3/3/3/3

24 h

4/4/4/4/4/4

3/3/3/3/3/3

4/4/4/4/4/4

3/3/3/3/3/3

48 h

4/4/4/4/4/4

3/3/3/3/3/3

4/4/4/4/4/4

3/3/3/3/3/3

72 h

4/4/4/4/4/4

3/4/3/3/3/3

4/4/4/4/4/4

3/4/3/3/3/4

Average 24h, 48h, 72h

4/4/4/4/4/4

3/3.33/3/3/3/3

4/4/4/4/4/4

3/3.33/3/3/3/3.33

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
In this study, Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) was corrosive to rabbit skin.
Executive summary:

In a primary dermal irritation study according to 40 CFR, Subdivision F, par. 158.50 and 158.135; Section 81-5, 6 New Zealand White rabbits were dermally exposed to 0.5 mL of Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) for 4 hours under semi-occlusive conditions.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

Severe erythema (grade 4) and moderate to severe edema (grade 3-4) were observed after 24 h – 72 h. Reversibility cannot be fully judged as erythema scores of 4 and edema scores of 3 – 4 were still present at the end of the observation period of 3 days. As all animals displayed severe blistering and eschar formation, no full reversibility after 21 days is assumed. Thus, the substance is considered to be corrosive.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: EPA 40 CFR, Par. 158.50 & 158.135, Subdivision F, Section 81-2, pp. 39 - 44, Nov. 1982
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: at least 2-3 kg
- Diet (e.g. ad libitum): rabbit diet, ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 65-75°F
- Humidity (%): 40-60%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg bw


Duration of treatment / exposure:
24 h
Observation period:
14 d
Number of animals:
5/sex
Details on study design:
OBSERVATION TIME POINTS
24, 72 h

SCORING SYSTEM:
Draize scale
Irritation parameter:
erythema score
Basis:
animal: 1-10
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
no observation after 48 h
Irritation parameter:
edema score
Basis:
animal: 1-10
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
no observation after 48 h
Irritant / corrosive response data:
The test item was corrosive to the skin (edema and erythema scores of 4 after 24 and 72 h). The skin sites were severely burned and discoloured black. The skin was thickened and stiff.
Other effects:
2/5 females died during the observation period. 5/8 surviving animals showed weight loss on day 14.
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
In an acute dermal toxicity study Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid was corrosive to rabbit skin.
Executive summary:

In an acute dermal toxicity study according to EPA 40 CFR, Par. 158.50 & 158.135, Subdivision F, Section 81-2, New Zealand White rabbits (5/sex) were dermally exposed to Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i) for 24 hours at a single dose of 2000 mg/kg bw in terms of test material (corresponding to 450 mg a.i./kg bw). Animals then were observed for 14 days.

2/5 females died during the observation period. 5/8 surviving animals showed weight loss on day 14.

The test item was corrosive to the skin (edema and erythema scores of 4 after 24 and 48 h). The skin sites were severely burned and discoloured black. The skin was thickened and stiff.

Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid was corrosive in this study.

 

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Version / remarks:
40CFR, Subdivision F, Par. 158.50 & 158.135, Section 81-4, pp. 51-55, November, 1982, Primary Eye Irritation
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-75
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Observation period (in vivo):
21 d
Duration of post- treatment incubation (in vitro):
n.a (treatment group without rinsing)
30 s (treatment group with rinsing)
Number of animals or in vitro replicates:
9 (6 without rinsing, 3 with rinsing)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): None for animals 1-6, after 30 seconds for animals 7- 9 (rinsing for 1 min with saline)

SCORING SYSTEM: Draize Scale

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal: 1-6
Remarks:
non-rinsed
Time point:
24/48/72 h
Score:
>= 3.33 - <= 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal: 7-9
Remarks:
rinsed
Time point:
24/48/72 h
Score:
>= 3.33 - <= 3.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal: 1-6
Remarks:
non-rinsed
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal: 7-9
Remarks:
rinsed
Time point:
24/48/72 h
Score:
1.67
Max. score:
2
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: 1-6
Remarks:
non-rinsed
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: 7-9
Remarks:
rinsed
Time point:
24/48/72 h
Score:
>= 2.67 - <= 3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: 1-6
Remarks:
non-rinsed
Time point:
24/48/72 h
Score:
>= 3.67 - <= 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: 7-9
Remarks:
rinsed
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
The test item produced severe redness and chemosis in 6 of 6 animals in the no rinse group and 3 of 3 animals in the rinse group. The test article produced severe irreversible corneal opacity and iritis in all test animals in both the no rinse and rinse groups. All animals in both test groups developed severe pannus by day 21. Rinsing did not prevent ocular damage.
Other effects:
The test article produced severe pannus in all animals in both the non-rinsed and rinsed groups.

Without rinsing

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

24 h

4/4/3/3/3/4

2/2/2/2/2/2

3/3/3/3/3/3

4/4/4/4/4/4

48 h

4/4/4/3/4/4

2/2/2/2/2/2

3/3/3/3/3/3

4/4/4/4/4/4

72 h

4/4/4/4/4/4

2/2/2/2/2/2

3/3/3/3/3/3

4/4/4/4/3/4

4 d

4/4/4/4/4/4

2/2/2/2/2/2

3/3/3/3/3/3

4/4/4/4/4/4

7 d

4/4/4/4/4/4

2/2/2/2/2/2

3/3/3/3/3/3

4/4/4/3/4/4

14 d

4/4/4/4/4/4

2/2/2/2/2/2

1/1/1/1/1/3

3/3/3/3/3/4

21 d

4/4/4/4/4/4

2/2/2/2/2/2

1/1/1/0/1/3

2/2/2/0/2/4

Average 24h, 48h, 72h

4/4/3.67/3.33/3.67/4

2/2/2/2/2/2

3/3/3/3/3/3

4/4/4/4/3.67/4

Reversibility

Not reversible

Not reversible

Not reversible

Not reversible

 

Eyes rinsed after 30 s

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

24 h

3/4/4

1/1/1

2/3/3

4/4/4

48 h

4/4/4

2/2/2

3/3/3

4/4/4

72 h

3/3/3

2/2/2

3/3/3

4/4/4

4 d

3/3/3

2/2/2

3/3/3

4/3/4

7 d

4/4/4

2/2/2

3/3/3

3/3/3

14 d

4/4/4

2/2/2

1/1/1

2/2/2

21 d

4/4/4

2/2/2

1/1/1

2/2/2

Average 24h, 48h, 72h

3.33/3.67/3.67

1.67/1.67/1.67

2.67/3/3

4/4/4

Reversibility

Not reversible

Not reversible

Not reversible

Not reversible

 

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In this study, Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) caused irreversible damage to the eye.
Executive summary:

In a primary eye irritation study according to EPA OPP 81-4, 0.1 mL of Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) was instilled into the conjunctival sac one eye of 9 New Zealand White rabbits. In 6 animals, the eyes were not rinsed after application, in 3 animals they eyes were rinsed for one minute with saline 30 seconds after application of the test item. Animals were then observed for 21 d.

The test item produced severe redness and chemosis in 6 of 6 animals in the no rinse group and 3 of 3 animals in the rinse group. The test article produced severe irreversible corneal opacity and iritis in all test animals in both the no rinse and rinse groups. All animals in both test groups developed severe pannus by day 21. Rinsing did not prevent ocular damage.

In this study, Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) caused irreversible damage to the eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In an acute dermal toxicity study according to EPA 40 CFR, Par. 158.50 & 158.135, Subdivision F, Section 81-2, New Zealand White rabbits (5/sex) were dermally exposed to Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i) for 24 hours at a single dose of 2000 mg/kg bw in terms of test material (corresponding to 450 mg a.i./kg bw). Animals then were observed for 14 days.

2/5 females died during the observation period. 5/8 surviving animals showed weight loss on day 14.

The test item was corrosive to the skin (edema and erythema scores of 4 after 24 and 48 h). The skin sites were severely burned and discoloured black. The skin was thickened and stiff.

Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid was corrosive in this study.

 

In a primary dermal irritation study according to 40 CFR, Subdivision F, par. 158.50 and 158.135; Section 81-5, 6 New Zealand White rabbits were dermally exposed to 0.5 mL of Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) for 4 hours under semi-occlusive conditions.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

Severe erythema (grade 4) and moderate to severe edema (grade 3-4) were observed after 24 h – 72 h. Reversibility cannot be fully judged as erythema scores of 4 and edema scores of 3 – 4 were still present at the end of the observation period of 3 days. As all animals displayed severe blistering and eschar formation, no full reversibility after 21 days is assumed. Thus, the substance is considered to be corrosive.

 

Eye irritation

In a primary eye irritation study according to EPA OPP 81-4, 0.1 mL of Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) was instilled into the conjunctival sac one eye of 9 New Zealand White rabbits. In 6 animals, the eyes were not rinsed after application, in 3 animals they eyes were rinsed for one minute with saline 30 seconds after application of the test item. Animals were then observed for 21 d.

The test item produced severe redness and chemosis in 6 of 6 animals in the no rinse group and 3 of 3 animals in the rinse group. The test article produced severe irreversible corneal opacity and iritis in all test animals in both the no rinse and rinse groups. All animals in both test groups developed severe pannus by day 21. Rinsing did not prevent ocular damage.

In this study, Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid (22.5% a.i.) caused irreversible damage to the eye.

 

Respiratory irritation

No data on the respiratory irritation of Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid are available. However, classification as “corrosive” implies, that the substance is also corrosive to the respiratory tract.

  

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

Justification for classification or non-classification

Based on reliable, adequate and relevant data, Reaction product of lauryl-PDA/lauryl-DETA with chloroacetic acid is classified as Category 1 (Causes severe skin burns and eye damage) according to CLP, EU GHS (Regulation (EC) No 1272/2008) and is assigned the hazard statement H314 and the signal word “Danger”.