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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
07 August 2013 to 26 August 2013 (in life phases)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study without deficiencies conducted on close structural analog
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
20 young females, approximately 9 weeks old, were group housed in Makrolon cages. Temperature was controlled (18-24 °C) and approxmately 70% humidity. Animals had free access to food and water.
Vehicle:
other:
Vehicle:
other:
Positive control substance(s):
yes
Remarks:
The six-month reliability check with Alpha-hexylcinnamicaldehyde indicates that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing for contact hypersensitivity.
Vehicle:
methyl ethyl ketone
Concentration:
0, 25, 50 and 100%
No. of animals per dose:
5
Details on study design:
Induction was carried out on days 1, 2 and 3 with application of 25 ul of material .
On Day 6, each animal was injected in the tail vein with 0.25 ml of sterile phosphate buffered saline containing 20 uCi of 3H-methyl thymidine.
After 5 hours exposure the mice were killed and the lymph node of each ear was excised.
Radioactivity measurements were performed using a Packard scintillation counter (2800TR).
Statistics:
Counting time was to a statistical precision of +/- 0.2% or a maximum of 5 minutes whichever came first.
Parameter:
SI
Remarks on result:
other: Group 1 (0%): 1.0 +/- 0.2 Group 2 (25%): 0.9 +/- 0.2 Group 3 (50%): 1.3 +/- 0.3 Group 4 (100%): 1.3 +/- 0.4
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Group 1 (0%): 236 +/- 36 Group 2 (25%): 215 +/- 19 Group 3 (50%): 308 +/- 38 Group 4 (100%): 315 +/- 70

A slight irritation was shown by the mice in the 100% dose group. It was judged of no toxicological significance which had no effect on the activity of the nodes.

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The substance is not a skin sensitiser.
Executive summary:

An assessment of contact hypersensitivity to Alkylated Naphthalene was made with the Mouse Local Lymph Node Assay. The study was carried out based on the guidelines described in:

OECD, Section 4, Health Effects, No.429 (2010),

EC, No 440/2008; B42: "Skin Sensitization: Local Lymph Node Assay"

EPA, OPPTS 870.2600 (2003) “Skin Sensitization”.

 

Test substance concentrations selected for the main study were based on the results of a pre-screen test.

 

In the main study, three experimental groups of five female CBA/J mice were treated with test substance concentrations of 25, 50 or 100% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Methyl ethyl ketone).

 

Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of Disintegrations Per Minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.

 

The slight irritation of the ears as shown by all animals treated at 100% was considered not to have a toxicologically significant effect on the activity of the nodes.

 

The majority of auricular lymph nodes were considered normal in size, except for the nodes of most animals treated at 50 and 100%.

No macroscopic abnormalities of the surrounding area were noted in any of the animals.

 

Mean DPM/animal values for the experimental groups treated with test substance concentrations 25, 50 and 100% were 215, 308 and 315 DPM respectively. The mean DPM/animal value for the vehicle control group was 236 DPM.

 

The SI values calculated for the substance concentrations 25, 50 and 100% were 0.9, 1.3 and 1.3 respectively.

 

Since there was no indication that the test substance elicited an SI3 when tested up to 100%, Alkylated Napthalene was considered to be a non skin sensitizer

 

The six-month reliability check with Alpha-hexylcinnamicaldehyde indicates that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing for contact hypersensitivity.

 

Based on these results, Alkylated Naphthalene would not be regarded as a skin sensitizer according to the recommendations made in the test guidelines. The test substance 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 (2011) and theRegulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

 

 

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

A GLP Mouse LLNA sensitisation study (OECD 429) was conducted with a close structural analog of alkylnaphthalene. The results showed the substance was not sensitising and does not require classification.

In addition, a sensitization study was obtained during the inquiry process that showed that a substance with the same EC number as Alkylnaphthalene was not sensitizing in an in vivo Buehler guinea pig study.


Migrated from Short description of key information:
A GLP LLNA sensitisation study (OECD 429) was conducted with a close structural analog of alkylnaphthalene. The results showed the substance was not sensitising.
In addition, a sensitization study was obtained during the inquiry process that showed that a substance with the same EC number as Alkylnaphthalene was not sensitizing in an in vivo Buehler guinea pig study.
The history of use of the product indicates no incidences of human sensitization.

Justification for selection of skin sensitisation endpoint:
The LLNA study cited was conducted with a close structural analog of Alkylnaphthalene (ref: alkylated naphthalene). The compounds differ only in a slight difference (2 carbons) of the alkyl chains.

Justification for classification or non-classification

Based on recommendations of OECD guideline, the substance would not be considered a skin sensitiser. The SI index was less than 2. Therefore, no classification is required according to CLP (Regulation EC No 1272/2008) or DSD (Directive 67/548/EEC.