Registration Dossier

Administrative data

Description of key information

2 of the 1092 patients tested showed allergic reactions to CAPB. Patch test reactions to cocamidopropyl betaine were difficult to interpret, owing to extremely common irritant reactions.

Based on this observation, Cocamidopropyl betaine can be considered to be a potentially weak skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to
Guideline:
other: patch test
Principles of method if other than guideline:
To describe patients with positive patch test reactions to cocamidopropyl betaine-related compounds in an occupational dermatology clinic
GLP compliance:
not specified
Type of study:
patch test
Justification for non-LLNA method:
not reported
Specific details on test material used for the study:
- Name of test material : 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts- Common Name: Cocamidopropyl betaine (CAPB)- Molecular formula: C19H38N2O3- Molecular weight: 342.52 g/mol- Smiles notation: CCCCCCCCCCCC(=O)NCCCN{+}(C)(C)CC(=O)O{-}- Substance type: Organic - Physical state: Solid
Species:
other: humans
Strain:
not specified
Details on test animals and environmental conditions:
Source: Finnish Institute of Occupational Health (FIOH)
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
1% in water
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
1%
Adequacy of challenge:
not specified
No. of animals per dose:
1092 patients
Details on study design:
the dermal reactions were read two or three times: on D2/D3/D4 or D2/D3/D6 or D2/D5, depending on the day of application
Challenge controls:
no data available
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1% in water
No. with + reactions:
2
Total no. in group:
1 092
Clinical observations:
+++/++ reactions were observed
Remarks on result:
positive indication of skin sensitisation

Patch test reactions to cocamidopropyl betaine (CAPB) and its impurities during 2002–2009 (1092 patients)

 test substance (provider, vehicle)

 Allergic

(++/+++/+++) reactions, n(%)

 irritant reactions

n(%)

 CAPB [Chemotechnique Diagnostics], water  2 (0.2)  166 (5)

cocamidopropyl betaine (CAPB)

Interpretation of results:
other: sensitizing
Conclusions:
2 of the 1092 patients tested showed allergic reactions to CAPB. Patch test reactions to cocamidopropyl betaine were difficult to interpret, owing to extremely common irritant reactions.Based on this observation, Cocamidopropyl betaine can be considered to be a potentially weak skin sensitizer.
Executive summary:

The aim of the study was to describe patients with positive patch test reactions to cocamidopropyl betaine-related compounds in an occupational dermatology clinic between 2002 -2009. Cocamidopropyl betaine[CAPB] was tested 1% in distilled water.

1092 patients were patch tested with Finn Chambers® according to the recommendations of the International Contact Dermatitis Research Group. The dermal reactions were read two or three times: on D2/D3/D4 or D2/D3/D6 or D2/D5, depending on the day of application. The patch test reactions were rated +/++/+++. 2 of the 1092 patients tested showed allergic reactions to CAPB. Patch test reactions to cocamidopropyl betaine were difficult to interpret, owing to extremely common irritant reactions.

Based on this observation, Cocamidopropyl betaine can be considered to be a potentially weak skin sensitizer.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In various studies,Cocamidopropyl betaine (CAPB)has been investigated for potential to cause dermal sensitizationto a greater or lesser extent. The studies are based on in vivo experiments in humans, guinea pigs for the target chemical. The results are summarized as follows:

The aim of the study was to describe patients with positive patch test reactions to cocamidopropyl betaine-related compounds in an occupational dermatology clinic between 2002 -2009. Cocamidopropyl betaine[CAPB] was tested 1% in distilled water.

1092 patients were patch tested with Finn Chambers® according to the recommendations of the International Contact Dermatitis Research Group. The dermal reactions were read two or three times: on D2/D3/D4 or D2/D3/D6 or D2/D5, depending on the day of application. The patch test reactions were rated +/++/+++. 2 of the 1092 patients tested showed allergic reactions to CAPB. Patch test reactions to cocamidopropyl betaine were difficult to interpret, owing to extremely common irritant reactions.

Based on this observation, Cocamidopropyl betaine can be considered to be a potentially weak skin sensitizer.

This is supported by the another study performed to analyse whether volunteers with previous positive patch tests to CAPB would react in provocative use tests of a product containing Cocamidoprpyl betaine [CAPB]. In order better to differentiate irritant response from allergic reactions and also in order to reconfirm panellists’ sensitivity towards CAPB , 10 male/female volunteers were patch tested with 0.1%, 0.3%, 1.0% dilutions of CAPB. A matched control group was used.

Readings took place at D2, D3 and D4 after application, using the following system:

NT = not tested; - = negative; ?+ = doubtful (minimal/marginal) reaction; + = weak (non-vesicular) reaction; ++ =  strong (oedematous or vesicular) reaction; +++ = extreme reaction; IR =  irritant reaction

Except for a + reaction to 1% CAPB, there was no reaction to patch tests in the control group With the CAPB-sensitized group, there was a little more reactivity. 5/10 showed clear + reactions to 1% CAPB (typically at D3), whilst a further 3 gave marginal and/or irritant reactions

The observed Reactions showed a typically crescendo pattern (with no reactions at D2 but reactions occurring by D3) suggesting a true allergic reaction.

Hence, Cocamidoprpyl betaine [CAPB] when used or tested above 1% can cause allergic reactions to humans.

 

These results are further supported by Patch tests performed on a total of 210 patients  with clinically suspected allergic contact dermatitis to skin-care products, as well as patients with dermatitis of the head and neck area to determine the allergic potential of Cocamidopropl betaine[CAPB].

The patients were patch-tested with a 1% aqueous solution of CAPB applied to small occluded patches on the backs of the patients for 48 h. Readings were performed at 48 h and at a later time, usually 96 h. Grading of reactions was done on a 0 to 3+ scale as used by the North American Contact Dermatitis Group. The grading scale for the patch test reactions was as follows:

− = no reaction; 1+ = redness,swelling; 2+ = redness, swelling, vesicles; 3+ = same as 2+ but spreading.

The patch test reactions were considered relevant to CAPB if the patient could identify one or more products containing CAPB that he or she had used before testing and if the dermatitis improved after the patient had avoided using the product. Of the 210 patients patch-tested, 12 had positive responses to CAPB, the subjects had reactions which showed up at either 48 or 96 h.

The possibility of Cocamidopropyl betaine [CAPB] being weak allergen to pre-sensitized humans can not be ruled out.

Hence, Cocamidopropyl betaine [CAPB] can be considered to be weak sensitizer to skin.

The above studies are also supported by a study performed according to Magnusson and Kligman method to study the capacity of Cocamidopropyl betaine to induce delayed type contact dermatitis in guinea pigs. 40 albino guinea pigs of both sex were distributed evenly into 2 groups- test and vehicle control.The concentrations of Cocamidopropyl betaine were as follows - Intradermal induction - 0.1% aqueous solution, Epicutaneous induction and challenge exposure - 10% aqueous solution. The induction exposure was a 2 step process- On day 1, guinea pigs were injected with 3 pairs of injections in an area of the back. The injections comprised of 0.1 ml FCA, 0.1ml test chemical without FCA, 0.1 ml test chemical in emulsified FCA. The control groiup were treated in the same way, where the test chemical was replaced with the vehicle.7 days later, the same area was clipped and test chemical was spread along an area of 2 -4 cm, covered with an impervious tape and the torso was firmly secured with an elastic bandage. The dressing was left in place for 48 h.

After 3 weeks of rest, the animals were subjected to challenge exposure. The flanks of the control and test animals were clipped, and occlusive patches of the test chemical and vehicle (control) were applied for 24 h. The test sites were evaluated for dermal reactions after 48 and 72 hours.

Macroscopic examination of the animals showed erythema, edema and inflammation in 8 of the 20 guinea pigs. Microscopic evaluation showed acanthosis and massive layer of infiltration of the superficial layers of the derma with lymphomonuclears in 2 animals. These appearances showed positive showed of sensitization.

Ambiguous reactions were observed in 4/20 animals.

Based on the reactions observed, Cocamidopropyl betaine can be considered to be sensitizing to skin.

The results of GPMT test and various patch test indicate a possibility that Cocamidopropyl betaine could have a potential to cause sensitization to skin.

Hence, Cocamidopropyl betaine can be considered to be weak sensitizer to skin.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Available data for Cocamidopropyl betaine (CAPB) indicates that it is likely to induce dermal reactions.

Hence,Cocamidopropyl betaine (CAPB) can be considered to be sensitizing to skin.