Registration Dossier

Administrative data

Description of key information

No sign of sensitisation was observed 24 and 48 hours after the challenge in a Guinea-Pig Maximisation Test performed according to OECD No. 406 test guideline on the structural analogue Cocamidopropyl hydroxysultaine as a 42% solution.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January-February 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP and OECD 406-compliant study, but no dose-range finding procedure is described and no positive control test substance was included whereas the 100% concentration tested was not irritant. In addition, no test substance batch number was reported.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of the registration dossier constitution, the skin sensitization study had already been performed according to Magnusson & Kligman method (report dated 1988).
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Extertal
- Age at study initiation: No data
- Weight at study initiation: 229-284 g
- Housing: max. 5 animals per Makrolon type IV cage (20 x 33 x 55 cm)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 2
- Humidity (%): 50-85
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12 (7.00 am-7.00 pm)

IN-LIFE DATES: From: 5 January 1988 To: 5 February 1988
Route:
intradermal and epicutaneous
Vehicle:
other: deionised water
Concentration / amount:
- Induction: 10%
- Challenge: 100%
Route:
epicutaneous, occlusive
Vehicle:
other: deionised water
Concentration / amount:
- Induction: 10%
- Challenge: 100%
No. of animals per dose:
20 test + 20 control animals
Details on study design:
RANGE FINDING TESTS: Two Guinea-pigs received a dermal application of the test item at 100% (0.5 mL per animal) under occlusive conditions.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal + topical)
- Exposure period: One week
- Test groups: One test group receiving test solution at 10% in deionised water, 10% in Freund's Complete Adjuvant (FCA) and undiluted FCA (0.05 mL per injection) [intradermal] + Undiluted test solution (0.5 mL) [topical]
- Control group: One control group receiving undiluted FCA, deionised water 10% in FCA and undiluted deionised water (0.05 mL per injection) [intradermal] + Deionized water (0.5 mL) [topical]
- Site: 2 injections sites arranged in pairs bilaterally to spinal column
- Frequency of applications: Topical induction 7 days after intradermal one
- Duration: Acute (intradermal) / 48 h (topical)
- Concentrations: 10% (intradermal) / 100% (topical)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 occlusive patch
- Day(s) of challenge: 3 weeks following intradermal induction
- Exposure period: 24 hours
- Test groups: Undiluted test solution (0.5 mL)
- Control group: Undiluted deionised water (0.5 mL)
- Site: Same as intradermal injection sites
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 hours after patch removal
Positive control substance(s):
no
Positive control results:
Not applicable
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
GHS criteria not met
Conclusions:
Cocamidopropyl hydroxysultaine, as a 42% solution, is not considered a skin sensitiser.
Executive summary:

In a Guinea-Pig Maximisation Test performed according to OECD No. 406 test guideline, Cocamidopropyl hydroxysultaine as a 42% solution was tested for its skin sensitising potential in Pirbright guinea pigs.

 

A preliminary test on two animals using the test solution at 100% showed that this concentration was appropriate for topical application. For the main test, 20 animals were applied the vehicle (deionised water) only (control group) and 20 other animals were applied the test substance. For the induction phase, animals received an intradermal injection of the test substance at 10% in deionised water or in Freund’s Complete Adjuvant (FCA) emulsion. One week later, a second induction was performed by a topical application of the test solution at 100%. Two weeks after the topical induction phase, challenge was performed by applying the test substance at 100% topically under occlusive conditions for 24 hours. Observation and grading of skin reactions was performed 24 and 48 hours after patch removal to assess potential sensitisation.

No skin reaction and therefore no sign of sensitisation was observed 24 and 48 hours after the challenge in any animal (control or treated groups).

Therefore, under the conditions of this test, Cocamidopropyl hydroxysultaine as a 42% solution is not considered as a skin sensitiser according to the criteria of Directive 67/548/EEC (DSD) or Regulation (EC) 1272/2008 (CLP).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
Total no. in group:
0
Clinical observations:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
GHS criteria not met
Conclusions:
By analogy with C8-18 Cocamidopropyl hydroxysultaine, C12-18 Cocamidopropyl hydroxysultaine is not considered a skin sensitiser.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

As the skin sensitisation potential of the substance EC 939-457-4 has not been investigated experimentally, a read-across approach was followed to fill in the endpoint based on a study conducted on the structural analogue substance C8 -18 cocamidopropyl hydroxysultaine (= source substance EC 939-455-3).

In a Guinea-Pig Maximisation Test performed according to OECD No. 406 test guideline, Cocamidopropyl hydroxysultaine as a 42% solution did not induce any skin reaction and therefore any sign of sensitisation 24 and 48 hours after the challenge in any animal following intradermal injection of the test substance at 10% and topical application of the test solution at 100% as induction, and challenge by applying the test substance at 100% topically under occlusive conditions for 24 hours.

 

The batch of test substance used contained less than 1% of free amidoamines (alkyl-amidopropyl dimethylamines). The synthesis of cocamidopropyl betaine or hydroxysultaine involves reaction of fatty acids derived from coconut oil with 3-dimethylaminopropylamine (DMAPA). In a second step, the resulting amidoamine is then reacted with either sodium chloroacetate or epichlorohydrin reacted with sodium bisulphite to give cocamidopropyl betaine ou hydroxysultaine, respectively. Both DMAPA and amidoamines, which may remain as synthesis impurities in the betaine or sultaine formulation, have been identified as sensitising impurities [for more details, see Human and Environmental Risk Assessment on ingredients of household cleaning products (HERA) on Cocamidopropyl betaine (CAPB, CAS No: 61789-40-0, 70851-07-9, 4292-10-8), Ed. 1.0, June 2005]. The concentration of these impurities should therefore remain as low as technically feasible.

 

The present animal study demonstrates that the active substance itself, cocamidopropyl hydroxysultaine, is devoid of skin sensitising potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the negative results obtained in a Guinea-Pig Maximization Test conducted on the structural analogue C8-18 Cocamidopropyl hydroxysultaine, the registered substance is not considered as a skin sensitiser according to the criteria of Regulation (EC) 1272/2008 (CLP)