Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 19 September 2012 to 8 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP study performed according to OECD Guideline 429, EC Method B42 and EPA method OPPTS 870.2600.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

EC Number:

272-789-1

EC Name:

Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

Cas Number:

68911-83-1

Molecular formula:

C40H76N2O

IUPAC Name:

Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: young adult animals: approximately 9 weeks old
- Weight at study initiation: between 20 and 23 g
- Housing: Group housing in labelled Makrolon cages containing sterilised sawdust as bedding material. Paper and shelters are used as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before the start of treatment under laboratory conditions. On day 6, the animals will be group housed in Makrolon MII type cages with a sheet of paper instead of sawdust and cage enrichment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): relative humidity of 40 to 70%
- Air changes (per hr): approximately 15 room air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

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 2.5, 5 or 10% w/w on three consecutive days, by open application on the ears.

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
Animals treated at 25%, 50% and 100% showed an increase in ear thickness > 25% indicating severe irritation. Moreover, animals at 100% showed moederate to severe erythema to slight eschar formation and ptosis. Animals treated at 10% showed slight erythema at day 3 only and variations in ear thickness of animals at 10% during the observation period were less than 25% from day 1 pre-dose values. No signs of systemic toxicity were observed in animals treated at 10%. Based on these results, the highest test substance concentration selected for the main study was 10%.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
-Interpretation of results:
An individual Stimulation Index (SI) is calculated for each animal. The individual SI is the ratio of the DPM/animal compared to the DPM/vehicle control group. A mean SI is calculated for each group using the individual SI values.
If the results indicate a SI >=3, the test substance should be regarded as a skin sensitizer.
Consideration was given to the EC3 value (the estimated test substance concentration that will give a SI = 3).

TREATMENT PREPARATION AND ADMINISTRATION:
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 or test substance and no correction was made for purity/composition of the test substance. Homogeneity was obtained to visually acceptable levels.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The six-month reliability check with alpha-hexylcinnamaldehyde indicates that the local lymph node assay as performed at the laboratory is an appropriate model for testing contact hypersensitivity.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

The SI values calculated for the substance concentrations 2.5, 5 and 10% were 3.8, 9.6 and 21.4 respectively. These results show that the test substance elicits and SI>=3. The data showed a dose-response and the EC3 value (the estimated test substance concentration that will give a SI=3) was established to be between 0 and 2.5%.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Mean DPM/animal values for the experimental groups treated with test substance concentrations 2.5, 5 and 10% were 876, 2202 and 4910 DPM respectively. the mean DPM/animal value for the vehicle control group was 229 DPM.

Any other information on results incl. tables

Based on the results:

- according to the recommendations made in the test guidelines, Reaction Product of Oleic acid, N1 -(9Z)-9-octadecen-1 -yl-1,3 -propanediamine and paraformaldehyde would be regarded as skin sensitizer.

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), Reaction Product of Oleic acid, N1 -(9Z)-9-octadecen-1 -yl-1,3 -propanediamine and paraformaldehyde should be classified as skin sensitizer (category 1).

- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures,

Oleic acid, N1 -(9Z)-9-octadecen-1 -yl-1,3 -propanediamine and paraformaldehyde should be classified as skin sensitizer (category 1) and labelled as H317: may cause an allergic skin reaction.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, reaction product of oleic acid, N1-(9Z)-9-octadecen-1-yl-1,3-propanediamine and paraformaldehyde was observed to be sensitising to the skin.