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Toxicological information

Skin sensitisation

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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

Referenceopen allclose all

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 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:
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

Reference
Name:
Unnamed
Type:
Constituent
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.