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Administrative data

Description of key information

The key study for dermal irritation (Liggett and Parcell 1986) examined the potential for the test substance to cause dermal irritation. Three rabbits were exposed to 0.5 ml of the test substance dermally for 4 hrs on clipped skin under a gauze pad held in place by an adhesive dressing. Examination of the treated skin was made approximately 30 minutes after removal of the patch and daily through 14 days. Grading and scoring of the dermal reactions was performed using the standard numerical scoring system. Irritation was noted in all animals at the first observation (maximum score of 2). Symptoms worsened, and desquamation, necrosis, and hyperkeratinization was noted by day 4. Symptoms resolved in one animal by day 12, but in the other two animals, symptoms were seen through the end of the observation period. The primary dermal irritation index was 2.17. The test substance is considered a Category 2 irritant according to CLP Regulation based on persistent irritation (H315: Causes skin irritation).

A key study for eye irritation (Liggett and Parcell 1986A) examined the potential of the test substance to cause irritation to eyes. Groups of three rabbits had 0.1 ml of test substance placed in each of their eyes. In one group, the eyes were not rinsed. In the second group, the eyes were rinsed after 4 seconds of exposure. In the third group, the eyes were rinsed after 30 seconds of exposure. Observations were made one hour and 1, 2, 3, 4, 7, 14, and 21 days after exposure. Severe irritation was noted in the animals whose eyes were not rinsed. This irritation was not resolved in one of these animals at the end of 21 days. Irritation was also seen in the animals rinsed after 30 seconds, although the irritation was not as severe, and the effects were fully reversible within 14 days. Mild irritation was seen in the animals rinsed after 4 seconds. These effects were fully reversible within 7 days. Since OECD guideline 405 for eye irritation studies calls for an exposure of at least 24 hrs, the results for unrinsed eyes were used for classification. According to these results, the test substance is a Category 1 eye irritant because it caused damage that was not reversible within 21 days (H318: Causes serious eye damage).

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:
key study
Study period:
March 18, 1986-March 31, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield Rabbits and Buckmasters
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2.7-3.3 kg
- Housing: individually housed in metal cages, identified by aluminum ear tags
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation: yes


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 degree C
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark


IN-LIFE DATES: From: March 18, 1986 To: March 31, 1986
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
0.5 ml aliquot of P-500 N-Na
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
Hair was clipped from a 10 x 10 area of the dorsal-lumbar region. Test substance was applied under a gauze pad, and then covered with elastic adhesive dressing. Examination of the treated skin was made approximately 30 minutes after removal of the patch and daily through 14 days. Grading and scoring of the dermal reactions was performed using the standard numerical scoring system.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
2.17
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
Well defined to moderate skin reactions were observed in all three animals following removal of the bandages. Desquamation of the stratum corneum was observed in all three animals. The reaction in all three animals gradually ameliorated from Days 5, 10 and 11, respectively, and had all resolved completely in one animal by Day 12.
Results of Skin Irritation Study

Day

Animal

1417

1491

1726

Erythema

Edema

Erythema

Edema

Erythema

Edema

0

2

1

2

2

2

1

1

2

2

2

3

2

3

2

2

2

2

1

2

2B

3

4

2A

2

1C

2

3B

4

4

2A

1

1C

2

3B

5

4

2A

1

1C

2

3B

6

4

3A

1

1C

2

3B

7

4

3A

1

1C

2

2B

8

4A

3C

1

1C

2

2B

9

2

2

1

1C

2B

2B

10

1

2

1

0

1

2

11

1

1

0

0

1

2

12

1

1

-

-

1

0

13

1

1

-

-

1

0

A ¿ Necrosis B ¿ Hyperkeratinization C ¿ Desquamation
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test substance was moderately to severely irritating to skin, but effects were not fully reversible within 14 days. The test substance is a Category 2 irritant according to EU GHS guidelines based on persistent irritation.
Executive summary:

This study examined the potential for the test substance to cause dermal irritation. Three rabbits were exposed to 0.5 ml of the test substance dermally for 4 hrs. The test substance was covered with an occlusive dressing and removed by washing 4 hrs later. Animals were examined at 30 minutes after removal, and daily thereafter for 14 days. Irritation was noted in all animals at the first observation (maximum score of 2). Symptoms worsened, and desquamation, necrosis, and hyperkeratinization was noted by day 4. Symptoms resolved in one animals by day 12, but in the other two animals, symptoms were seen through the end of the observation period. The primary dermal irritation index was 2.17. The test substance is considered a Category 2 irritant according to EU GHS guidelines based on persistent irritation.

Endpoint:
skin irritation: in vitro / ex vivo
Remarks:
In vitro / ex vivo / other data on skin irritation / corrosion not available; study not required based on availability of more definitive in vivo data.
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 24, 1986-May 12, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield Rabbits and Buckmasters
- Age at study initiation: 9-13 weeks
- Weight at study initiation: 2.1-3.1 kg
- Housing: individually housed in metal cages, identified by aluminum ear tags
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation: yes


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 degree C
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark


IN-LIFE DATES: From: March 24, 1986 To: May 12, 1986
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1 mL aliquot of P-500 N-Na
Duration of treatment / exposure:
For three rabbits the eyelids were then gently held together for one second before releasing.
For three other rabbits the eyes were irrigated with water for 5 minutes following a 4-second exposure.
For the remaining three rabbits the eyes were irrigated for 5 minutes following a 30-second exposure.
Observation period (in vivo):
Eyes were examined after 1 hour and 1, 2, 3, 4, 7, 14 and 21 days after exposure.
Number of animals or in vitro replicates:
9
Details on study design:

SCORING SYSTEM: Draize scale
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1.75
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: not rinsed
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: rinse after 4 seconds
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1.06
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: rinsed after 30 seconds
Irritant / corrosive response data:
The following results were noted:
1) Three animals without any rinsing:  averaged irritation scores (24, 48, 72 hours) for each animal: cornea 2.3, 1.7, 2; iris: 1.3, 0, 0; conjunctivae redness: 3, 1.7, 2; conjunctivae chemosis: 3, 2, 2.  In the first animal the effects were persistent at day 21.
2) Three animals with rinsing for five minutes following a 30 second exposure: averaged scores: cornea 0.7, 1, 1.3; iris: 0, 0.7, 0.3; conjunctivae redness: 1.7, 2, 1.3; conjunctivae chemosis: 2, 1.3, 2.  The eyes were normal 7 or 14 days after instillation.
3) Three animals with rinsing for five minutes following a 4 second exposure: averaged scores: cornea 0.7, 2.3, 0.7; iris: 0, 0, 0; conjunctivae redness: 1.7, 1.7, 1; conjunctivae chemosis: 1.3, 2, 1.  The eyes were normal 7 days after instillation.

Findings lead to a definition of irritating for LAS at 47% applied without rinsing, irritating (even if with lower effects, mainly as cornea opacity and conjunctivae redness) with rinsing after 30 second of exposure, and not irritating with rinsing after 4 second of exposure.
Results of Eye Irritation Study ¿ No Rinsing

Hours

Days

Animal

1

24

48

72

4

7

14

21

1

Cornea

2

1

2

4

3B

3B

3BC

3BC

Iris

0

1

1

2

1

1

1

0

Conjunctiva - Erythema

1

3

3

3

3

3

2

1

Conjunctiva ¿ Chemosis

2

3

3

3

3

2

2

1

2

Cornea

1

1

2

2

2

1

0

Iris

0

0

0

0

0

0

0

Conjunctiva - Erythema

1

1

2

2

1

0

0

Conjunctiva ¿ Chemosis

1

2

2

2

1

0

0

3

Cornea

1

2

2

2

2

1

0

Iris

0

0

0

0

1

0

0

Conjunctiva - Erythema

1

2

2

2

2

1

0

Conjunctiva ¿ Chemosis

1

2

2

2

2

0

0

Results of Eye Irritation Study ¿ Rinsing after 4 Seconds

Hours

Days

Animal

1

24

48

72

4

7

1

Cornea

0

0

1

1

1

0

Iris

0

0

0

0

1

0

Conjunctiva - Erythema

1

2

2

1

2

0

Conjunctiva ¿ Chemosis

2

2

1

1

1

0

2

Cornea

0

2

3

2

0

0

Iris

0

0

0

0

0

0

Conjunctiva - Erythema

1

2

2

1

2

0

Conjunctiva ¿ Chemosis

2

2

2

1

1

0

3

Cornea

0

1

0

1

1

0

Iris

0

0

0

0

0

0

Conjunctiva - Erythema

1

1

1

1

2

0

Conjunctiva ¿ Chemosis

2

1

1

1

1

0

Results of Eye Irritation Study ¿ Rinsing after 30 Seconds

Hours

Days

Animal

1

24

48

72

4

7

14

1

Cornea

0

1

0

D

D

1

0

Iris

0

0

0

0

0

0

0

Conjunctiva - Erythema

1

2

2

1

1

1

0

Conjunctiva ¿ Chemosis

2

1

1

0

0

0

0

2

Cornea

0

1

1

1

2

0

Iris

0

0

1

1

0

0

Conjunctiva - Erythema

1

2

2

2

2

0

Conjunctiva ¿ Chemosis

2

1

2

1

1

0

3

Cornea

0

1

2

1

2A

2AB

0

Iris

0

0

0

1

1

1

0

Conjunctiva - Erythema

1

1

1

2

2

2

0

Conjunctiva ¿ Chemosis

2

2

2

2

1

1

0

A ¿ Loss of Corneal Epithelium

B ¿ Vascularization

C ¿ Pannus

D ¿ Dulling of the Cornea

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
When not rinsed, damage to the eyes due to the test substance was not reversed within 21 days. According to EU GHS guidelines the test substance is a category 1 eye irritant.
Executive summary:

This study examined the potential of the test substance to cause irritation to eyes. Groups of three rabbits had 0.1 ml of test substance placed in each of their eyes. In one group, the eyes were not rinsed. In the second group, the eyes were rinsed after 4 seconds of exposure. In the third group, the eyes were rinsed after 30 seconds of exposure. Observations were made one hour and 1, 2, 3, 4, 7, 14, and 21 days after exposure. Severe irritation was noted in the animals whose eyes were not rinsed. This irritation was not resolved in one of these animals at the end of 21 days. Irritation was also seen in the animals rinsed after 30 seconds, although the irritation was not as severe, and the effects were fully reversible within 14 days. Mild irritation was seen in the animals rinsed after 4 seconds. These effects were fully reversible within 7 days. Since OECD guideline 405 for eye irritation studies calls for an exposure of at least 24 hrs, the results for unrinsed eyes were used for classification. According to these results, the test substance is a category 1 eye irritant because it caused damage that was not reversible within 21 days.

Endpoint:
eye irritation: in vitro / ex vivo
Remarks:
In vitro / ex vivo / other data on eye irritation / corrosion not available; study not required based on availability of more definitive in vivo data.
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

LAS is irritating to both the skin and eyes of test animals. In skin, irritation symptoms worsened, and desquamation, necrosis, and hyperkeratinization were noted by day 4 in all animals. These resolved in one animal by day 12, but in the other two animals symptoms continued through the end of the observation period. Therefore, LAS is considered a Category 2 skin irritant. In eyes, severe irritation was noted in the animals whose eyes were not rinsed and was not resolved by day 21. Milder irritation was observed in animals that had the test substance rinsed from their eye after 4 or 30 seconds, and effects seen in these rinsed animals were reversible within 7 or 14 days. Based on the irreversible irritation observed in the unrinsed animals, LAS is considered a Category 1 eye irritant.

Justification for classification or non-classification

A study comparable to OECD guideline 404 found that the test substance is considered a Category 2 irritant according to EU GHS guidelines based on persistent irritation.

A study comparable to OECD guideline 405 found the test substance is a category 1 eye irritant based on EU GHS guidelines.

Effects on skin irritation/corrosion:irritating
Effects on eye irritation:irritating
Effect level:emptyEndpoint conclusion:Adverse effect observed