4-[[5-[[[4-(aminocarbonyl)phenyl]amino]carbonyl]-2-methoxyphenyl]azo]-N-(5-chloro-2,4-dimethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide

Endpoint summary

Description of key information

A local lymph node assay was performed according to OCED 429 using test item concentrations of 2.5, 5 and 10% (w/v) suspended in propylene glycol.

The animals (4 female mice/dose grouop) did not show any clinical signs during the course of the study and no cases of mortality were observed. In this study Stimulation Indices (S.I.) of 0.87, 1.19 and 1.04 were determined with the test item at concentrations of 2.5, 5 and 10% (w/v) in propylene glycol, respectively. The results obtained with the positive control confirmed the validity of the test.

The test item was not a skin sensitiser in this assay.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 29 SEP 2005 to 18 OCT 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 429), GLP compliant

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands, Horst, The Netherlands
- Age at study initiation: 6-9 weeks
- Weight at study initiation: 18.3-22.5 g
- Housing: single
- Diet: pelleted standard diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: yes (acclimatisation period not given)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-74
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

propylene glycol

Concentration:

0 %, 2.5 %, 5 %, 10 % (w/v)

No. of animals per dose:

4 females per dose group
2 females in the pre-test

Details on study design:

RANGE FINDING TESTS:
- non GLP
- Compound solubility: 10 % (w/v) was the highest concentration at which the test item could be suspended (in propylene glycol) so that an applicable test item formulation was obtained.
- Irritation: no irritation effects were observed at these concentrations after a single application.
- Lymph node proliferation response: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: 1: exposure to at least one concentration of the test item resulted in an incorporation of 3H-methyl thymidine at least 3-fold or greater than that recorded in control mice as indicated by the stimulation index
2: data are compatible with a conventional dose response, although allowance must be made for either local toxicity or immunological suppression

TREATMENT PREPARATION AND ADMINISTRATION:
- individual preparation of weight volume dilutions using a magnetic stirrer as homogenizer
- 25 µl were spread over the entire dorsal surface of each ear lobe once daily for three consecutive days

Positive control substance(s):

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

Statistics:

- calculation of mean values and standard deviations for body weight .

Positive control results:

Stimulation indices of 1.05, 1.71 and 3.30 were determined with the positive control substance at concentrations of 5%, 10% and 25% (w/v), respectively, in acetone:olive oil (4+1). An EC3 value of 22.2 % (w/v) was calculated.

Parameter:

SI

Value:

ca. 1.04

Test group / Remarks:

Concentration 10%

Parameter:

SI

Value:

ca. 1.19

Test group / Remarks:

Concentration 5%

Parameter:

SI

Value:

ca. 0.87

Test group / Remarks:

Concentration 2.5%

Remarks on result:

other:

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: The DPM were measured for the pooled lymph nodes of each treatment group (8 lymph nodes per dose group): Background: 27.24 dpm Control group: 2949.37 dpm 2.5 % test item: 2574.18 dpm 5 % test item: 3512.97 dpm 10 % test item: 3078.41 dpm

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. The body weight of the animals was within the normal range. Calculation of the EC3 value was not performed, because no test concentration produced a SI of 3 or higher.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was not sensitising in this LLNA in concentrations up to 10 % (w/v) in propylene glycol, the highest technically achievable concentration.

Executive summary:

In the study the test item suspended in propylene glycol was assessed for its possible contact allergenic potential.

For this purpose a local lymph node assay was performed according to OCED 429 using test item concentrations of 2.5, 5 and 10% (w/v).

The animals (4 female mice/dose grouop) did not show any clinical signs during the course of the study and no cases of mortality were observed. In this study Stimulation Indices (S.I.) of 0.87, 1.19 and 1.04 were determined with the test item at concentrations of 2.5, 5 and 10% (w/v) in propylene glycol, respectively. The results obtained with the positive control confirmed the validity of the test.

The test item was not a skin sensitiser in this assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No classification, as no adverse effetcs observed.