Sodium 2-amino-4,6-dinitrophenoxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

OPINION on Picramic acid and sodium picramate COLIPA n° B28

Author:

European Commission

Year:

2011

Bibliographic source:

Scientific Committee on Consumer Safety SCCS, COLIPA B28; last updated 2012

Reference 2

Reference Type:

publication

Title:

Amended Safety Assessment of Sodium Picramate and Picramic Acid

Author:

Lillian C. Becker, Wilma F. Bergfeld, Donald V. Belsito, Curtis D. Klaassen, JamesG.Marks Jr, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, and F. Alan Andersen

Year:

2009

Bibliographic source:

International Journal of Toxicology; 28(Suppl 3); 205S-216S, 2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

To determine the dermal sensitization potential of the test chemical in mice according to LLNA method

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 2-amino-4,6-dinitrophenoxide

EC Number:

212-603-8

EC Name:

Sodium 2-amino-4,6-dinitrophenoxide

Cas Number:

831-52-7

Molecular formula:

C6H5N3O5.Na

IUPAC Name:

sodium 2-amino-4,6-dinitrophenoxide

Test material form:

solid

Details on test material:

Name of the test chemical: sodium 2-amino-4,6-dinitrophenolate
Common name: Sodium picramate
Molecular Weight: 221.104 g/mol
Molecular Formula: C6H4N3O5Na
SMILES Notation: C1=C(C=C(C(=C1[N+](=O)[O-])[O-])N)[N+](=O)[O-].[Na+]
InChI:1S/C6H5N3O5.Na/c7-4-1-3(8(11)12)2-5(6(4)10)9(13)14;/h1-2,10H,7H2;/q;+1/p-1
Substance type: Organic
Physical State: Solid

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/CaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

mice, CBA/CaOlaHsd (nulliparous and non-pregnant)

Study design: in vivo (LLNA)

Vehicle:

dimethyl sulphoxide

Concentration:

0, 1, 5, 10, 25 and 50% w/v

No. of animals per dose:

24 females (4 per group)

Details on study design:

Sodium picramate (1%,
5%, 10%, 25%, or 50% test chemical in DMSO) was applied to both ears of the mice (n ¼ 4) for 3 consecutive days. The control group was administered the vehicle only. Two days after the last application,
the mice were injected with radiolabeled thymidine (methyl-3H-thymidine). The mice were killed approximately 5 hours after the injection, and the draining auricular lymph nodes were excised and pooled per group. The concentration of the radiolabel was measured.

EC3 is the estimated concentration of a chemical necessary to cause a 3-fold increase in lymph node cell proliferative activity. Chemicals that at 1 or more test concentrations provoke a 3-fold or greater in lymphnode cell proliferation compared with vehicle controls are classified as potential contact allergens.

Positive control substance(s):

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

Statistics:

EC3 is the estimated concentration of a chemical necessary to cause a 3-fold increase in lymph node cell proliferative activity. Chemicals that at 1 or more test concentrations provoke a 3-fold or greater in lymphnode cell proliferation compared with vehicle controls are classified as potential contact allergens.

Results and discussion

Positive control results:

The calculated EC3 value for the test chemical was 6.7% w/v. For the positive control, α- hexylcinnamaldehyde was 12.96%.

In vivo (LLNA)

Results

Key result

Parameter:

EC3

Value:

6.7

Test group / Remarks:

test group

Remarks on result:

other: positive sensitizer

Cellular proliferation data / Observations:

The Stimulations Indices[SI] were 1.2, 2.7, 3.6, 7.9 and 11.4 for the concentrations 1%,5%,10%,25%, 50% respectively.
The calculated EC3 value for the test chemical was 6.7% w/v

Any other information on results incl. tables

Results of the LLNA study

Concentration	Stimulation Index
Test item
1%	1.2
5%	2.7
10%	3.6
25%	7.9
50%	11.4
Alpha-hexylcinnamaldehyde
5%	0.87
10%	2.26
25%	6.01

Applicant's summary and conclusion

Interpretation of results:

other: sensitizing

Conclusions:

The Stimulations Indices[SI] were 1.2, 2.7, 3.6, 7.9 and 11.4 for the concentrations 1%,5%,10%,25%, 50% respectively.
The calculated EC3 value for the test chemical was 6.7% w/v. For the positive control, α- hexylcinnamaldehyde was 12.96%.
Based on the above findings the test chemical can be considered to be sensitiziing to skin.

Executive summary:

The dermal sensitization potential of the test chemical was assessed in mice according to LLNA method. The study was conducted as per OECD Guidelines 429.

5%, 10%, 25%, or 50% test chemical in DMSO) was applied to both ears of female non pregnant, nulliparous CBA/CaOlaHsd mice (n= 4) for 3 consecutive days. The control group was administered the vehicle only. Two days after the last application, the mice were injected with radiolabeled thymidine (methyl-3H-thymidine). The mice were killed approximately 5 hours after the injection, and the draining auricular lymph nodes were excised and pooled per group. The concentration of the radiolabel was measured.

EC3 is the estimated concentration of a chemical necessary to cause a 3 -fold increase in lymph node cell proliferative activity. Chemicals that at 1 or more test concentrations provoke a 3-fold or greater in lymphnode cell proliferation compared with vehicle controls are classified as potential contact allergens.

The Stimulations Indices[SI] were 1.2, 2.7, 3.6, 7.9 and 11.4 for the concentrations 1%,5%,10%,25%, 50% respectively.

The calculated EC3 value for the test chemical was 6.7% w/v and 12.96% for the positive control, α- hexylcinnamaldehyde.

Based on the above findings the test chemical can be considered to be sensitiziing to skin.