Registration Dossier

Administrative data

Description of key information

When tested for skin irritation in vivo, Cocamidopropyl hydroxysultaine as a 16% solids (registered substance C12 -18 cocamidopropyl hydroxysultaine)or 41.5% solution (analogue substance C8 18 cocamidopropyl hydroxysultaine), was not irritating.
When tested for eye irritation in vivo at concentrations ranging from 10% solids to 41.5%, Cocamidopropyl hydroxysultaine induced ocular damage that was persistent at the end of the observation period (7 to 21 days) in some animals. The registed substance C12 -18 Cocamidopropyl hydroxysultaine is therefore considered a severe eye irritant.

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:
supporting study
Study period:
27 February 1989 - 2 March 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Abraded and nonabraded skin instead of intact skin used, exposure period of 24 hours instead of 4 hours, occlusive dressing instead of semi-occlusive, observations conducted up to 72 hours instead of 14 days, not conducted at the 48 h timepoint
Qualifier:
according to
Guideline:
other: modification of Section 1500.41 of the Code of Federal Regulations
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: clipped, then abraded and nonabraded sites used
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
3 (2M + 1F)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24/72 h
Score:
0.5
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #2
Score:
0.5
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 2472 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24/72 h
Score:
0.5
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation

Animal number

Erythema / Eschar

Edema

24 h

72 h

Individual score

24 h

72 h

Individual score

Intact skin

8173M

1

0

0.5

0

0

0

8174M

1

0

0.5

0

0

0

8175F

2

0

1

1

0

0.5

 

Mean score

0.7

Mean score

0.2

Abraded skin

8173M

1

0

0.5

0

0

0

8174M

1

0

0.5

0

0

0

8175F

2

0

1

1

0

0.5

 

Mean score

0.7

Mean score

0.2

Details of skin irritation scores (according to Draize scale)

Interpretation of results:
study cannot be used for classification
Conclusions:
Cocamidopropyl hydroxysultaine, as a 16% solids solution, is not considered a skin irritant.
Executive summary:

Cocamidopropyl hydroxysultaine, as a 16% solids aqueous solution, has been tested for acute skin irritation on 2 male and one female New Zealand White rabbits, in accordance with procedures of section 1500.41 of US Code of Federal Regulations, 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 clipped area of the abraded and non-abraded skin (appr. 10% of the skin surface), for 24 hours under an occlusive dressing. Cutaneous examinations were performed at 24 and 72 hours after the application.

 

At removal of the dressing, very slight erythema was observed in the 2 males at the abraded and non-abraded skin sites, and a well-defined erythema (score 2) was observed in the female at both skin sites. No oedema was observed in the male rats, whereas the female presented a very slight oedema.

No cutaneous reactions were observed in any of the animals at 72 hours, at both the abraded and non-abraded skin sites.

 

Based on these results, Cocamidopropyl hydroxysultaine, as a 16% solids aqueous solution, was not considered a skin irritant.

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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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 C12-18 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 = C12-18 cocamidopropyl hydroxysultaine (EC 939-457-4)

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:
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 vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
12-19 May 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
7-day observation period instead of 21 days
Qualifier:
according to
Guideline:
other: modification of the US Code of Federal Regulations 1500-42 (1985)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
single instillation (lids gently held together for 1 second before releasing them to prevent loss of test material)
Observation period (in vivo):
Ocular reactions graded at 24, 48, 72 hours, 4 and 7 days after instillation
Number of animals or in vitro replicates:
3 males
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.78
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.78
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.78
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.78
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
other: conjunctival discharge
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.56
Max. score:
3
Reversibility:
not fully reversible within: 7 days

Animal number

24 h

48 h

72 h

4 d

7 d

Individual score*

Cornea

7844

2

2

2

2

2

2

7845

2

2

1

0

0

1.67

7846

2

2

1

0

0

1.67

 

Mean score

1.78

Iris

7844

1

1

1

1

0

1

7845

1

1

1

0

0

1

7846

1

0

0

0

0

0.33

 

Mean score

0.78

Conjunctival redness

7844

2

2

2

1

1

2

7845

2

2

2

1

0

2

7846

2

1

1

1

0

1.33

 

Mean score

1.78

Conjunctival chemosis

7844

2

2

2

1

1

2

7845

3

2

1

1

1

2

7846

2

1

1

1

0

1.33

 

Mean score

1.78

Conjunctival discharge

7844

2

2

1

1

1

1.67

7845

3

2

1

1

0

2

7846

1

1

1

0

0

1

 

Mean score

1.56

* 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 10% solids solution (pH 7.0), is considered a severe eye irritant.
Executive summary:

Cocamidopropyl hydroxysultaine, as a 10% solids solution (pH 7.0), has been tested for ocular irritation on 3 New-Zealand White rabbits, according to US Code of Federal Regulations1500-42 (1985), and in compliance with Good Laboratory Practice.

The test article was instillated, in a single dose of 0.1 mL, into the conjunctival sac of the right eye of each animal. The left eye remained untreated and served as a control. The eyes were not rinsed. Ocular examinations were performed 24, 48 and 72 hours, then on day 4 and 7 after instillation.

 

Corneal opacity (score 2) on a relatively large area was observed at 24 hours in the three rabbits. This reaction was no longer present at day 4 in two of the rabbits, but was still present at day 7 in the third one. The mean scores (24-48-72 hours) calculated for each animal were 2.0 - 1.67 - 1.67 for corneal opacity.

Iridial changes were observed at 24 hours in all the animals, then until 72 hours in one rabbit, and day 4 in another one. The mean scores (24-48-72 hours) calculated for each animal were 1.0 - 1.0 - 0.33 for iris reaction.

Conjunctival irritation (redness and chemosis) was observed throughout the observation period in two of the animals with decreasing intensity, while signs were no longer present at day 7 in the third one. The mean scores (24-48-72 hours) calculated for each animal were 2.0 - 2.0 - 1.33 for both redness and chemosis. In addition, conjunctival discharge was observed in all the animals.

 

Ocular effects were below classification criteria of Annex VI of the Directive 67/548/EEC for R41 classification, but complete reversibility was not assessed. Considering the persistence of eye damages at the end of the observation period (7 days), Cocamidopropyl hydroxysultaine, as a 10% solids solution (pH 7.0), was considered a severe eye irritant.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
12-19 May 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
7-day observation period instead of 21 days
Qualifier:
according to
Guideline:
other: modification of the US Code of Federal Regulations 1500-42 (1985)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
single instillation (lids gently held together for 1 second before releasing them to prevent loss of test material)
Observation period (in vivo):
Ocular reactions graded at 24, 48, 72 hours, 4 and 7 days after instillation
Number of animals or in vitro replicates:
3 (2M + 1F)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
1
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.45
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
other: conjunctival discharge
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.56
Max. score:
3
Reversibility:
not fully reversible within: 7 days

Animal number

24 h

48 h

72 h

4 d

7 d

Individual score*

Cornea

8167M

2

2

2

2

2

2

8168M

2

2

2

2

1

2

8169F

2

2

2

2

0

2

 

Mean score

2

Iris

8167M

1

1

1

1

1

1

8168M

1

1

1

0

0

1

8169F

0

0

0

0

0

0

 

Mean score

0.67

Conjunctival redness

8167M

3

3

3

3

3

3

8168M

3

3

2

1

0

2.67

8169F

2

2

1

1

0

1.67

 

Mean score

2.45

Conjunctival chemosis

8167M

2

2

2

2

2

2

8168M

3

2

1

0

0

2

8169F

1

1

1

1

0

1

 

Mean score

1.67

Conjunctival discharge

8167M

3

3

2

2

2

2.67

8168M

3

3

1

0

0

2.33

8169F

3

3

2

1

0

2.67

 

Mean score

2.56

* 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 16% solids solution (pH 7.0), is considered a severe eye irritant.
Executive summary:

Cocamidopropyl hydroxysultaine, as a 16% solids solution (pH 7.0), has been tested for ocular irritation on 3 New-Zealand White rabbits, according to US Code of Federal Regulations1500-42 (1985), and in compliance with Good Laboratory Practice.

The test article was instillated, in a single dose of 0.1 mL, into the conjunctival sac of the right eye of each animal. The left eye remained untreated and served as a control. The eyes were not rinsed. Ocular examinations were performed 24, 48 and 72 hours, then on day 4 and 7 after instillation.

 

Corneal opacity (score 2) on a relatively large area was observed at 24 hours in all of the rabbits. This reaction persisted until day 4 in 1/3 rabbits and day 7 in 2/3. The mean scores (24-48-72 hours) calculated for each animal were 2.0 - 2.0 - 2.0 for corneal opacity.

Iridial alterations (score 1) were observed in two animals, and the reaction persisted until up to day 7 in one animal, whereas it was no longer present at day 4 in the other. The mean scores (24-48-72 hours) calculated for each animal were 1.0 - 1.0 - 0.0.

Conjunctival redness (score 2 to 3) was observed at 24 hours and persisted until day 7 (score 3) in one rabbit, and day 4 in the two others (score 1). Chemosis was observed throughout the observation period with varying intensity depending on the animals. The mean scores (24-48-72 hours) calculated for each animal were 3.0 - 2.67 - 1.67 for redness and 2.0 - 2.0 - 1.0 for chemosis. In addition, significant conjunctival discharge was observed in all the animals at 24 and 48 hours, decreasing in intensity thereafter.

 

Considering the persistence of corneal damages at the end of the observation period (7 days), Cocamidopropyl hydroxysultaine, as a 16% solids solution (pH 7.0), should be considered a severe eye irritant.

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:
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 C12-18 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 = C12-18 cocamidopropyl hydroxysultaine (EC 939-457-4)

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:
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 (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

As the local effects of the registered substance C12 -18 cocamidopropyl hydroxysultaine were assessed only with diluted substances, studies conducted in the structural analogue substance C8 -18 cocamidopropyl hydroxysultaine (= source substance EC 939-455-3) were used to complete the dataset and assess the skin and eye irritation potential of the registered substance. 

Skin irritation:

C8 -18 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.

In another study (Klimisch score 2, 1989), used as supportive, the registere substance C12 -18 Cocamidopropyl hydroxysultaine had been applied to rabbits at 16% solids under occlusive conditions for 24 hours, either to intact or abraded skin. Whatever conditions, very slight erythema and/or edema were observed, which were 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:

The structural analogue C8 -18 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.

In two other studies (Klimisch score 2, 1988 or 1989), used as supportive, C12 -18 Cocamidopropyl hydroxysultaine had been instillated in rabbit eyes at 10% or 16% solids, the animals being observed for up to 7 days. Although the period of observation was not extended up to 21 days, corneal opacity and conjunctival redness, chemosis or discharge were still observed in some animals 7 days after instillation. The severity of the ocular findings was concentration-related.


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 16% solids or 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 7 -day or 21 -day observation period following instillation of concentrations ranging from 10% solids to 41.5%, 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).