Registration Dossier

Administrative data

Description of key information

When tested for skin irritation in vivo, the structural analogue Cocamidopropyl hydroxysultaine as a 41.5% solution, was not irritating. By analogy, the registered substance Lauramidopropylhydroxysultaine is considered not irritating to skin.
When tested for eye irritation in vivo at concentrations of 41.5%, the analogue Cocamidopropyl hydroxysultaine induced ocular damage that was persistent at the end of the observation period (7 to 21 days) in some animals. Cocamidopropyl hydroxysultaine is therefore considered a severe eye irritant. Furthermore, an in vitro test on chorioallantoic membrane of Hen's egg performed on the commercial product containing the registered substance at ca. 42% (commercial product diluted at 1.25% in the in vitro test) confirmed the severe eye irritating potential of the registered substance.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
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:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 May 1995 - 27 July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: accredited supplier
- Gender: male
- Age upon arrival at test facility: approx. 9-10 weeks
- Weight at study initiation: 2.3 - 2.4 kg
- Housing: individually in stainless steel cages (48 x 59 x 37 cm) with grilled floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 50-85
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 30 May 1995 To: 16 June 1995
Type of coverage:
semiocclusive
Preparation of test site:
shaved
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 hours
Observation period:
72 hours after the end of exposure period (examinations at 60 min, 24, 48 and 72 h)
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm²
- Type of wrap if used: substance placed on 2.5 x 2.5 cm surgical gauze, patch held close to the skin using adhesive tape strips, strip of gauze wrapped around trunk of the animal using additional adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): once patch removed, remainder of product eliminated with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
See table below

Animal number

Erythema / Eschar

Edema

60 min

24 h

48 h

72 h

Individual score*

60 min

24 h

48 h

72 h

Individual score*

146

1

0

0

0

0

0

0

0

0

0

912

1

0

0

0

0

0

0

0

0

0

913

1

1

1

0

0.67

0

0

0

0

0

 

Mean score

0.22

Mean score

0

* For the 24, 48 and 72 h timepoints

Details of skin irritation scores (according to Draize)

Interpretation of results:
GHS criteria not met
Conclusions:
Cocamidopropyl hydroxysultaine, as a 41.5% solution, is not considered a skin irritant.
Executive summary:

Cocamidopropyl hydroxysultaine, as a 41.5% solution, has been tested for acute skin irritation on 3 male New Zealand White rabbits, in accordance with OECD test guideline 404, and in compliance with Good Laboratory Practice.

The test article was applied as such in a single dermal dose of 0.5 mL to a shaved 6 cm² area of the intact skin, for 4 hours under a semi-occlusive dressing. Cutaneous examinations were performed at 1, 24, 48 and 72 hours after the dressing removal.

One hour after dressing removal, very slight erythema (grade 1) was observed in all animals. At examinations carried out 24 and 48 h after dressing removal, only one animal showed very slight erythema (grade 1).

No cutaneous reactions were observed in any of the animals at 72 hours after dressing removal.

Mean scores for erythema and edema (24, 48 and 72 hours after treatment) were 0.22 and 0.00, respectively.

 

Based on these results, Cocamidopropyl hydroxysultaine, as a 41.5% solution, was not considered a skin irritant.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C8-C18 AAPHS and C12 AAPHS have the same functional groups, and general composition. The main variable resides in the alkyl chain distribution.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical = C8-18 cocamidopropyl hydroxysultaine (EC 939-455-3)
Target chemical = C12 cocamidopropyl hydroxysultaine (EC 242-893-1)

3. ANALOGUE APPROACH JUSTIFICATION
The alkyl C-chain distribution of the source chemical significantly overlaps with the one of the target chemical, the C12-alkyl derivative being the major constituent in both chemicals. The structural differences in side C-chains is not expected to lead to significant differences on phys-chem properties.

4. DATA MATRIX: see "Documentation and scientific justification of the read-across approach" in section 13.2
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
C8-18 Cocamidopropyl hydroxysultaine, as a 41.5% solution, is not considered a skin irritant. By analogy, C12-18 Cocamidopropyl hydroxysultaine is not considered a skin irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 04 DEcember 2008 to 05 January 2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented meeting accepted scientific principles, acceptable for assessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Hen's Egg Test - Utilizing the Chorioallantoic Membrane (HET-CAM). The test is a modification of that described by Kemper and Luepke (Kemper, F.M. & Luepke, N.P., (1986). The HET-CAM Test: An Alternative to the Draize Test. FD Chem. Toxic. 24, p. 495 - 496.).
The chick embryo has been used extensively in toxicology. The chorioallantoic membrane (CAM) of the chick embryo is a complete tissue with organoid elements from all germ cell layers. The chorionic epithelium is ectodermal and the allantoic epithelium is endodermal. The mesoderm located between these epithelia is a complete connective tissue including arteries, capillaries, veins and lymphatic vessels. The CAM responds to injury with a complete inflammatory reaction, comparable to that induced in the rabbit eye test. It is technically easy to study, and is without nerves to sense pain.
GLP compliance:
no
Species:
other: White Leghorn eggs
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Moyer's Chicks, Inc., in Quakertown, Pennsylvania, USA
- Age at study initiation: up to 7 days (stored at 13°C +/- 3°C)
- Weight at study initiation: not applicable
- Housing: For incubation the eggs were placed, on their sides, in a Kuhl, humidified incubator. The incubator is such that the eggs are automatically rotated once every hour. The eggs were incubated for 10 days. On day eight (8) the eggs were turned so that the acutely angled end faced down.
- Diet (e.g. ad libitum): not applicable
- Water (e.g. ad libitum): not applicable
- Acclimation period: not applicable

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 37° C (+/- 2° C)
- Humidity (%): not applicable
- Air changes (per hr): not applicable
- Photoperiod (hrs dark / hrs light): not applicable

IN-LIFE DATES: From: To: not applicable
Vehicle:
not specified
Controls:
other: reference articles: Johnson's Baby Shampoo (diluted at 50%) and Head & Shoulders Shampoo (diluted at 50%)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.3 mL
- Concentration (if solution): 1.25%
Duration of treatment / exposure:
20 seconds
Observation period (in vivo):
All CAM's were observed immediately prior to test article administration and at 30 seconds, two and five minutes after exposure to the test article.
Number of animals or in vitro replicates:
4 CAMs were used for each conditions (test item, reference articles)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test or reference article was rinsed from each CAM with 5 mL of physiological saline.
- Time after start of exposure: immediately after the end of the 20 seconds exposure period.

SCORING SYSTEM: The reactions of the CAM, the blood vessels, including the capillaries, and the albumin were examined and scored for irritant effects as detailed in the table 7.3.2/1. The numerical, time dependent scores were totaled for each CAM. Each reaction type can be recorded only once for each CAM, therefore the maximum score per CAM is 32. The mean score was determined for all CAM's similarly tested. Each article was then classified as indicated in the table 7.3.2/2.

TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
other: Average CAM score
Value:
12
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
other: see details in Table 7.3.2/3

Table 7.3.2/3: Results of the HET-CAM test

Substance

CAM #

Scores

 

 

 

0.5 min

2 min

5 min

Total

Mackam LSB-50 (1.25%)

1

5  7

0

0

12

2

5  7

0

0

12

3

5  7

0

0

12

4

5  7

0

0

12

Average

12.00

Reference article Johnson's Baby shampoo (50%)

1

5  7

0

0

12

2

5  7

0

0

12

3

0

3  5

0

8

4

5  7

0

0

12

Average

11.00

Reference article Head & Shoulders shampoo (50%)

1

5  7

0

5  7

24

2

5  7

0

5  7

24

3

5  7

7

0

19

4

5  7

0

5

17

Average

21.00

 

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
Under the test conditions, the test item Mackam LSB-50 diluted at 1.25% (vehicle unknown) induced moderate irritating effects on the chorioallantoic membrane of Hen's Egg.
Executive summary:

In an in vitro test on Chorioallantoic Membrane of Hen's Egg (HET-CAM test), 0.3 mL of Mackam LSB-50 diluted at 1.25% (vehicle unknown) was applied for 20 seconds on 4 Chorioallantoic Membranes from White Leghorn Hen’s egg. At the end of the exposure period, membranes were washed with physiological saline and observation of the membrane was done at 30 seconds, 2 and 5 minutes after the end of exposure. Different parameters such as Hyperemia, minimal hemorrhage (“feathering”), hemorrhage (obvious leakage) and coagulation and/or thrombosis were assessed and scored for each CAM at each time observation point. The mean score was determined for all CAM's similarly tested.

Two reference articles were also tested: Johnson's Baby Shampoo and Head & Shoulders Shampoo, both diluted at 50%.

The mean score for the CAM exposed to the test item Mackam LSB-50 diluted at 1.25% was 12.00 (max achievable score of 32.00). The mean score obtained for the CAM treated with the reference article Jonhson's baby shampoo at 50% was 11.00 (considered as moderate irritant) whereas the one obtained for the second reference article Head & Shoulders shampoo at 50% was 21.00 (considered as severe irritant).

Under the test conditions, the test item Mackam LSB-50 diluted at 1.25% induced moderate irritating effects on the chorioallantoic membrane of Hen's Egg. It can be assumed that the undiluted test item Mackam LSB-50 (containing the registered substance at ca. 42%) would induce more severe irritating effects. Therefore the classification as severe irritating to eyes (Eye Dam. 1, H318) of the registered substance, pure lauramidopropylhydroxysultaine, is warranted.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 May 1995 - 28 July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: B&K Universal G.J., Barcelona, Spain
- Gender: male
- Age upon arrival at test facility: approx. 9-10 weeks
- Weight at study initiation: 2.2 - 2.4 kg
- Housing: individually in stainless steel cages (48 x 59 x 37 cm) with grilled floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 50-85
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 30 May 1995 To: 27 June 1995
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 males
Details on study design:
ADMINISTRATION OF TEST SUBSTANCE
- Location: into the right conjunctival sac, made accessible by carefully pulling lower lid down
- Procedure immediately after instillation: lids of treated eye held closed for approx. 10 sec

OBSERVATION TIMEPOINTS: 1, 24, 48, 72 hours, and on day 7, 14 and 21 after instillation

SCORING SYSTEM: Draize scoring on conjunctivae, iris and cornea (as per OECD test guideline 405 recommendations)

TOOL USED TO ASSESS SCORE:
- Use of hand-slit lamp / biomicroscope: not specified
- Use of fluorescein: for all observations except 1 h after instillation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
probability of mild irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of mild irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
See table below

Animal number

1 h

24 h

48 h

72 h

7 d

14 d

21 d

Individual score*

Cornea

299

0

1

1

1

1

1

0

1

289

0

1

1

1

0

0

0

1

190

0

1

1

1

0

0

0

1

 

Mean score

1

Iris

299

1

1

1

1

1

0

0

1

289

1

1

1

1

1

0

0

1

190

1

1

1

1

0

0

0

1

 

Mean score

1

Conjunctival redness

299

3

3

3

2

1

0

0

2.67

289

2

3

3

3

2

1

0

3

190

2

3

3

2

1

1

0

2.67

 

Mean score

2.78

Conjunctival chemosis

299

2

2

1

1

1

1

0

1.33

289

3

3

2

2

1

0

0

2.33

190

2

2

2

2

1

1

1

2

 

Mean score

1.89

* For the 24, 48 and 72 h timepoints

Details of eye irritation scores (according to Draize)

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Cocamidopropyl hydroxysultaine, as a 41.5% solution, is considered a severe eye irritant.
Executive summary:

Cocamidopropyl hydroxysultaine, as a 41.5% solution (Betadet SHR), has been tested for acute eye irritation on 3 male New Zealand White rabbits, in accordance with OECD test guideline 405, and in compliance with Good Laboratory Practice.

The test article was applied as such in a single conjunctival dose of 0.1 mL in the right eye of each rabbit, the untreated eye being used as a control. Ocular examinations, grading cornea, iris and conjunctiva (redness and chemosis) reactions, were performed at 1, 24, 48, 72 hours, and on day 7, 14 and 21 after instillation of the test article.

Within the first hour following instillation, the test article induced conjunctival abnormalities including hyperhaemia ranging from grade 2 (diffuse, crimson color, individual vessels not easily discernible) to grade 3 (diffuse, deep red color), edema ranging from grade 2 to 3, redness of the bulbar conjunctivae, lacrimation and congestion and injection of the iris (grade 1).

At the observations carried out 24, 48 and 72 hours after instillation, all rabbits showed hyperhaemia ranging from grade 2 to grade 3, chemosis from grade 1 to grade 3, redness of the bulbar conjunctivae, lacrimation and congestion and injection of the iris (grade 1). Corneal opacity (grade 1) was also observed in all animals.

Some of the corneal and conjunctival abnormalities persisted up to day 14 after instillation inclusive. Conjunctival chemosis was still observed in one of the rabbits 21 days after instillation of the test article.

 

Based on these results, Cocamidopropyl hydroxysultaine, as a 41.5% solution, was considered a severe eye irritant.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C8-C18 AAPHS and C12 AAPHS have the same functional groups, and general composition. The main variable resides in the alkyl chain distribution.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical = C8-18 cocamidopropyl hydroxysultaine (EC 939-455-3)
Target chemical = C12 cocamidopropyl hydroxysultaine (EC 242-893-1)

3. ANALOGUE APPROACH JUSTIFICATION
The alkyl C-chain distribution of the source chemical significantly overlaps with the one of the target chemical, the C12-alkyl derivative being the major constituent in both chemicals. The structural differences in side C-chains is not expected to lead to significant differences on phys-chem properties.

4. DATA MATRIX: see "Documentation and scientific justification of the read-across approach" in section 13.2
Reason / purpose for cross-reference:
read-across source
Number of animals or in vitro replicates:
3 males
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
probability of mild irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 21 d
Remarks on result:
probability of mild irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21
Remarks on result:
probability of severe irritation
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Based on conjunctival chemosis still observed in one rabbit 21 days after instillation
Conclusions:
C8-18 Cocamidopropyl hydroxysultaine, as a 41.5% solution, is considered a severe eye irritant. By analogy, C12-18 Cocamidopropyl hydroxysultaine is considered as a severe eye irritant.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Only one RIPT test in human and one in vitro HET-CAM assay are available on the registered substance. In the absence of studies conducted according to OECD guidelines, a read-across was therefore performed with the cocamidopropyl hydroxysultaine which contains alkylamidopropylhydroxysultaine with carbon chain from C8 to C18. The main component of Cocamidopropylhydroxysultaine C8-18 is lauramidopropylhydroxysultaine. Justification for the read-across is documented in a separate document attached in Iuclid Section 13.

Skin irritation:

Cocamidopropyl hydroxysultaine was tested in vivo in a Klimisch score 2 study (1995), used as a key study. In this study, the test substance was applied to rabbits at 41.5% under semi-occlusive conditions for 4 hours. Very slight erythema was observed, which was fully reversible within 72 hours.

This correlates with the results of Repeated Insult Patch Tests in healthy human volunteers (see section 7.10.3. Direct observations), where the repeated dermal application of a 12% aqueous solution of Lauramidopropylhydroxysultaine to 54 healthy volunteers did not result in any skin reaction indicative of irritation.

Eye irritation:

Cocamidopropyl hydroxysultaine was tested in vivo in a Klimisch score 2 study (1995), used as a key study. In this study, the test substance was instillated at 41.5% in the eyes of rabbits observed for up to 21 days. Corneal and conjunctival injuries persisted for up to day 14 inclusive in some animals. Conjunctival chemosis was still observed in one of the rabbits 21 days after instillation.

An in vitro test on chorioallantoic membrane of Hen's egg was available on the registered substance itself and used as supporting study. In this test, a solution at 1.25% of the commercial product containing the registered substance induced moderate irritating effects of the membrane, confirming therefore that the pure registered substance is considered as severe eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Recent GLP and OECD test guideline-compliant study (Klimisch score 2)

Justification for selection of eye irritation endpoint:
Recent GLP and OECD test guideline-compliant study (Klimisch score 2)

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation:

Based on the data available on Cocoamidoproplhydroxysultaine and Lauramidopropylhydroxysultaine, the registered substance does not need to be classified for skin irritation.

Eye irritation:

Based on the data available on Cocoamidoproplhydroxysultaine and Lauramidopropylhydroxysultaine, the registered substance

needs to be considered a severe eye irritant and classified accordingly as Eye damage 1, H318 (according to Reg. 1272/2008 (CLP) criteria).