Silver docosanoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, a weight of evidence analysis was performed prior to start of this study. All available information was evaluated (e.g. existing human and animal data, literature, substance data supplied by the sponsor, analysis of structure activity relationships (SAR), physicochemical properties and reactivity (pH, buffering capacity).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Silver docosanoate

EC Number:

219-641-4

EC Name:

Silver docosanoate

Cas Number:

2489-05-6

Molecular formula:

C22H44O2.Ag

IUPAC Name:

silver(1+) docosanoate

Constituent 2

Reference substance name:

CH03220

IUPAC Name:

CH03220

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): CH03220
- Molecular formula (if other than submission substance): C22H4402.Ag
- Molecular weight (if other than submission substance):447.44
- Physical state: white powder
- Analytical purity: 100 wt % silver docosanoate
- Lot/batch No.: CH03220/AJ
- Storage condition of test material: at room temperature, protected from light
- Stability under storage conditions: stable
- Expiry date: 25 nov 2012 (1 year after receipt of the test substance)

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Mouse, CBA/J strain, inbred, SPF-Quality. Recognized by the international guidelines as the recommended test system (e.g. OECD, EC, EPA). Source: Janvier, Le Genest-Saint-Isle, France
20 females (nulliparous and non-pregnant), five females per group
Young adult animals (approx. 11 weeks old) were selected. Body weight variation was within +/- 20% of the sex mean.

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

10, 25 and 40%

No. of animals per dose:

5

Details on study design:

Three groups of five animals were treated with one test substance concentration per group. The highest test substance concentration was selected from the pre-screen test. One group of five animals was treated with vehicle.

Positive control substance(s):

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

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Mean DPM/animal values for the experimental groups treated with test substance concentrations 10, 25 and 40% were 943, 838 and 651 DPM respectively. The mean DPM/animal value for the vehicle control group was 390 DPM.

Results 2

Parameter:

SI

Value:

2.4

Variability:

0.7

Test group / Remarks:

10% test substance

Results 3

Parameter:

SI

Value:

2.1

Variability:

0.8

Test group / Remarks:

25% test substance

Results 4

Parameter:

SI

Value:

1.7

Variability:

0.6

Test group / Remarks:

40% test substance

Results 5

Parameter:

SI

Value:

1

Variability:

0.4

Test group / Remarks:

0% test substance

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

CHO322O would not be regarded as a skin sensitzer according to the recommandations 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 GHS.

Executive summary:

Assessment of Contact Hypersensitivity to CH03220 in 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 10, 25 or 40% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Acetone/Olive oil (4:1 v/v)). Three days after the last exposure,all animals were injected with H-methylthymidine 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.

No irritation of the ears was observed in any of the animals examined. White test substance remnants were present on the dorsal surface of the ears of both animals at 25 and 40% (Days 1, 2 and 3), which did not hamper scoring of the skin reactions.

All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. 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 10, 25 and 40% were 943, 838 and 651 DPM respectively. The mean DPM/animal value for the vehicle control group was 390 DPM.

The SI values calculated for the substance concentrations 10, 25 and 40% were 2.4, 2.1 and 1.7 respectively.

Since there was no indication that the test substance elicits an SI≥3 when tested up to 40%, CH03220 was considered not to be a skin sensitizer. It was established that the EC3 value (the estimated test substance concentration that will give a SI =3) (if any) exceeds 40%.

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

Based on these results, CH03220 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 the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.