1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C8-18(even numbered) acyl) derivs., hydroxides, inner salts

Endpoint summary

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).