Registration Dossier

Administrative data

Description of key information

When tested for skin irritation in vivo, Cocamidopropyl hydroxysultaine as a 41.5% solution, was not irritating.
When tested for eye irritation in vivo as a 41.5% solution, Cocamidopropyl hydroxysultaine induced ocular damage that was persistent at the end of the observation period (21 days) in some animals. Cocamidopropyl hydroxysultaine is therefore considered a severe eye irritant.

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:
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: 72h
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
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, 0, 0.67 and 0, 0 and 0 in each animal, respectively.

 

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

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:
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 days
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
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 days
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 days
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 days
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 days
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 days
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 days
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 days
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 days
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 days
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 conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Cocamidopropyl hydroxysultaine was tested in vivo in a Klimisch score 1 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 a Repeated Insult Patch Test in healthy human volunteers (see section 7.10.3. Direct observations), where the repeated dermal application of a 2.5% aqueous solution of C8 -C18 amidopropylhydroxysultaine to 44 healthy human volunteers under occlusive conditions did not result in any skin reaction indicative of irritation.

Eye irritation:

Cocamidopropyl hydroxysultaine was tested in vivo in a Klimisch score 1 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.


Justification for selection of skin irritation / corrosion endpoint:
Recent GLP and OECD test guideline-compliant study (Klimisch score 1)

Justification for selection of eye irritation endpoint:
Recent GLP and OECD test guideline-compliant study (Klimisch score 1)

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation:

No relevant signs of skin irritation were noted in rabbits at concentrations of 41.5%. Therefore, Cocamidopropyl hydroxysultaine as a pure substance does not need to be classified for skin irritation.

Eye irritation:

Due to the persistence of ocular damage in some rabbits at the end of a 21-day observation period following instillation of a 41.5% solution, Cocamidopropyl hydroxysultaine as a pure substance needs to be considered a severe eye irritant and classified accordingly as Eye damage 1, H318 (according to Reg. 1272/2008 (CLP) criteria).