Registration Dossier

Administrative data

Description of key information

The skin sensitization potential of the registration substance was evaluated according to OECD TG 406 protocol using the guinea pig maximization methode of Magnusson and Kligman. Based on the results, the registration substance is not a 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
Study period:
2014
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
No validated LLNA available at time of study implementation. Available data from an guinea pig maximization test scientifically adequate.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Species: Albino guinea pig, Dunkin Hartley strain, (SPF-quality). Recognized by international guidelines as the recommended test system
(e.g. OECD, EC).
Source: Charles River France, L’arbresle Cedex, France
Number of animals: Experimental group: 10 females. Control group: 5 females. (females were nulliparous and non-pregnant).
Age: Young adult animals (approx. 4-6 weeks old) were selected.
Identification: Ear tattoo.
Health inspection: At least prior to dosing. It was ensured that the animals were healthy and
that the skin to be treated was intact and free from any abnormality.

Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40
to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any
variations to these conditions were maintained in the raw data and had no effect on the outcome of the
study.
Accommodation
Group housing of maximally 5 animals per labeled Noryl cage (Tecniplast; 74 cm x 54 cm x 25 cm
height) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France and
from 27th November 2013 onwards: Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG,
Rosenberg, Germany) and shelters (CS3B02A Play tunnels (90 mm x 5 mm x 125 mm), Datesand,
Manchester, UK) as cage enrichment. The acclimatization period was at least 5 days before the start
of treatment under laboratory conditions.
Diet
Complete maintenance diet for guinea pigs (SSNIFF® Spezialdiäten GmbH, Soest, Germany). In
addition, hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least twice a week.
Water
Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed
according to facility standard procedures. There were no findings that could interfere with the study.
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
induction: intradermally injected with a 50% concentration
induction: epidermally exposed to a 100% concentration
challenge: 100%
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
induction: intradermally injected with a 50% concentration
induction: epidermally exposed to a 100% concentration
challenge: 100%
No. of animals per dose:
Experimental group: 10 females.
Control group: 5 females.
Details on study design:
The test substance formulations (w/w) were prepared within 4 hours prior
to each treatment. No adjustment was made for specific gravity of the
vehicle. Homogeneity was obtained to visually acceptable levels. No
correction was made for purity/composition of the test substance.
A preliminary irritation study was conducted in order to select test substance concentrations to be
used in the main Study. Ffive animals were selected. The starting- and subsequent concentrations were
taken from the series: 100% (undiluted), 50%, 20%, 10%, 5%, 2%, 1% in corn oil as vehicle.
The test system and procedures were identical to those used during the main study.
Positive control substance(s):
yes
Remarks:
Alpha- Hexylcinnamaldehyde
Positive control results:
The skin reactions observed in all experimental animals in response to the 20% positive control substance
concentration in the challenge phase were considered indicative of sensitisation, since these
responses were absent or less severe in the control group. These results lead to a sensitization
rate of 90 per cent to the 20% positive control substance concentration.
From these results, it was concluded that the female guinea pig of the Dunkin Hartley strain is
an appropriate animal model for the performance of studies designed to evaluate the sensitizing
potential of a substance in a Maximization type of test.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% corn oil
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% corn oil
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
20% alpha-Hexylcinnamaldehyde
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
none
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
only scaliness observed in one animal
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these results N-(2-Ethylhexyl)-isononan-1-amide does not have to be classified as sensitizer and has no
obligatory labelling requirement for sensitization by skin contact according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United
Nations (2007) (including all amendments),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures
(including all amendments).
Executive summary:

Assessment of potential contact hypersensitivity to N-(2-Ethylhexyl)-isononan-1-amide in the albino guinea pig was carried out based on OECD test guideline 406 using the maximization method of Magnusson and Kligman in its most recent revision. The test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, ten experimental animals were intradermally injected with a 50% concentration and epidermally exposed to a 100% concentration. Five control animals were similarly treated, but with vehicle alone (corn oil). Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 100% test substance concentration and the vehicle. Scaliness was observed on the test substance treated skin area for one experimental animal at 48 hours after removal of the dressing. No skin reactions were evident in the other experimental animals and in control animals. The skin reactions (only scaliness) observed in response to a 100% test substance concentration in one (of the ten) experimental animals in the challenge phase were considered indicative of sensitization, based on the absence of any response in the control animals. These results indicate a conservatively judged sensitization rate of 10 per cent. Based on these results N-(2-Ethylhexyl)-isononan-1-amide does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to the: - Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) (including all amendments), - Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)

Justification for classification or non-classification

The registration substance is not a skin sensitizer based on the results from a GPMT according to OECD TG 406. Also no sensitizing potential was revealed based on computational based structure alert analysis. None of the available toxicological data and known exposure conditions indicates concern that the registration substance may possess respiratory sensitization properties. Based on all available data the registered substance is not a sensitiser and therefore is not subject for classification and labelling requirements with regard to this endpoint.