Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
June 1, 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was equivalent to OECD Guideline 406.
Reason / purpose:
reference to same study
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
No information on reliability check. Induction concentration could have been higher: 0.2% caused slight erythema in 1 of the two animals in the range finding test. However, the study is still considered sufficient for the hazard identification.
GLP compliance:
no
Type of study:
Buehler test
Test material information:
Composition 1
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Redfern Animal Breeders, Jasons Farm, Old Hay, Brenchley, Kent, UK
- Weight at study initiation: Young, withing range 300 – 400 g
- Sex: Male and female
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
For the determination of a non-irritating concentration: 0.1, 0.2, 0.5, 1.0, 5.0, 10 and 20.0 % w/v (0.4 ml was applied over 6 h)
Dermal induction: 1000 µg test substance / ml (0.4 ml, 0.1 % w/v) for 6 h under closed patches
Challenge: 400 µg test substance/ml (0.4 ml, 0.1 % w/v) for 6 h under closed patches on untreated other flank.
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
For the determination of a non-irritating concentration: 0.1, 0.2, 0.5, 1.0, 5.0, 10 and 20.0 % w/v (0.4 ml was applied over 6 h)
Dermal induction: 1000 µg test substance / ml (0.4 ml, 0.1 % w/v) for 6 h under closed patches
Challenge: 400 µg test substance/ml (0.4 ml, 0.1 % w/v) for 6 h under closed patches on untreated other flank.
No. of animals per dose:
Dose range finding: 16 animals (8 groups of 2 animals)
Treatment group: 20 animals (10 male, 10 female)
Controlgroup: 10 animals (5 male, 5 female)

Results for dose range finding study:

Skin reactions were scored after 24 h. Results:
20%: severe erythema 2/2;
10%: severe erythema 2/2;
 5%: severe- moderate 2/2;
 1%: severe- moderate 4/4;
0.5%: moderate-slight 2/2;
0.2%: slight erythema 1/2;
0.1%: No erythema 2/2.

Results for main study:

First grading: 0/20 (3/20 showed a grade of 0.5; in control 2/10 showed a grade 0.5). Second grading: 0/20 (no erythema was observed in any of the animals)

The test substance tested has a narrower chain length distribution compared to full coco. The results from this substance however are fully valid for evaluation of TMAC as:

- The tested substance constitutes already for 70% TMAC, without some additional shorter and longer chain lengths present..

Principally, aspects of sensitisation are related to possible reactivity and protein binding, which are properties that are independent to chain length.
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the Buehler test, the substance is considered to be non-sensitizing.
Executive summary:

A study equivalent to the Buehler test protocol (OECD Guideline 406) was conducted to determine the sensitising potential of the read-across substance C12-18 TMAC (test conducted on C12-14 alkyl trimethyl ammonium chloride). The chain length distribution of the test substance is narrower than C12-18 TMAC, however, the study is considered valid to assess this endpoint, because the tested substance is a constitute of C12-18 TMAC (at 70%), without some additional shorter and longer chain lengths present, and principally, aspects of sensitisation are related to possible reactivity and protein binding, which are independent of chain length. A pre-test was conducted to determine non-irritating concentrations to use in the main study. For the main study the induction was carried out at: topical 0.1% w/v in aqueous ethanol for 6 hours, repeated after 7 and 14 days. Challenge was done two weeks after the last induction treatment (Day 28): control and test animals received 0.1% w/v in acetone for 6 hours on previously untreated site under closed patches. After 18 hours the sites were treated with depilatory cream, rinsed and dried. After 3 hours, challenge sites were evaluated for erythema on a scale of 0-3. Evaluation was repeated 24 hours later. Results of the first grading were: 0/20 (3/20 showed a grade of 0.5; in control 2/10 showed a grade 0.5). Second grading: 0/20 (no erythema was observed in any of the animals). Under the conditions of the Buehler test, the test substance was not sensitizing.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A study equivalent to the Buehler test protocol (OECD Guideline 406) was conducted to determine the sensitising potential of the read-across substance C12-18 TMAC (test conducted on C12-14 alkyl trimethyl ammonium chloride). The chain length distribution of the test substance is narrower than C12-18 TMAC, however, the study is considered valid to assess this endpoint, because the tested substance is a constitute of C12-C18 TMAC (at 70%), without some additional shorter and longer chain lengths present, and principally, aspects of sensitisation are related to possible reactivity and protein binding, which are independent of chain length. A pre-test was conducted to determine non-irritating concentrations to use in the main study. For the main study the induction was carried out at: topical 0.1% w/v in aqueous ethanol for 6 hours, repeated after 7 and 14 days. Challenge was done two weeks after the last induction treatment (Day 28): control and test animals received 0.1% w/v in acetone for 6 hours on previously untreated site under closed patches. After 18 hours the sites were treated with depilatory cream, rinsed and dried. After 3 hours, challenge sites were evaluated for erythema on a scale of 0-3. Evaluation was repeated 24 hours later. Results of the first grading were: 0/20 (3/20 showed a grade of 0.5; in control 2/10 showed a grade 0.5). Second grading: 0/20 (no erythema was observed in any of the animals). Under the conditions of the Buehler test, the test substance was not sensitizing (Jones JR, 1978).


Migrated from Short description of key information:
No skin sensitisation reactions were observed in a Buehler test on C12-14 TMAC. C12-14 ADMAES is also not expected to be a skin sensitiser.

Justification for selection of skin sensitisation endpoint:
Reliable guideline study available on a read-across substance.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

As respiratory sensitisers also elicit positive results in predictive tests for contact sensitisation, a negative outcome for dermal sensitisation is also predictive for the respiratory pathway. Furthermore, the substance is a sticky solid with a low vapour pressure. Due to it physical state and physico-chemical properties, it is unlikely that it will form inhalable dust, mist or fumes when handled and used in solid form. In case inhalable forms of the substance (either pure or in aqueous solutions) are created under particular conditions (e.g., spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.

Justification for classification or non-classification

No skin sensitisation reactions were observed in a guinea pig Buehler test with the read-across substance C12-14, therefore, no classification is required for sensitisation according to Directive 67/548/EEC and Regulation EC 1272/2008.