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Diss Factsheets

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:
other: well performed GLP and OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guideline
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)

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate
EC Number:
278-575-4
EC Name:
Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate
Cas Number:
76918-62-2
Molecular formula:
C18H13N3O3.Na
Details on test material:
- Name of test material (as cited in study report): Naphtolon-Na TF

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
-strain: CBA/CaOlaHsd
- Source: Harlan Netherlands
- Age at study initiation: 7-8 weeks (beginning of acclimatization)
- Weight at study initiation: 18.7 g to 23.9 g
- Housing: single caging, Makrolon Type I, with wire mesh top, granulated soft wood bedding
- Diet (e.g. ad libitum): Pelleted standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): artificial light 6.00 a.m. - 6.00 p.m.

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
0 (control), 5, 10 and 25 % (w/v)
No. of animals per dose:
4 animals per treatment group, 4 animals in the control group
Details on study design:
RANGE FINDING TESTS:
- Compound solubility:
To determine the highest non-irritant test concentration or the highest technically applicable concentration, a pretest was performed in two mice.
The data showed that the highest test item concentration, which could be technically used was a 25 % suspension in DMF.
Also in other vehicles used, e.g DMSO, ethanol, propylene glycol a higher concentrations could not be suspended.
- Irritation:
At this concentration the treated mouse did not show any signs of severe local irritation or systemic toxicity.
The test item in the main study was, therefore, assayed at 5, 10, 25 %.



MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Pooled (4 animals/group) LLNA
- Criteria used to consider a positive response:
A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled:
- First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
- Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.


TREATMENT PREPARATION AND ADMINISTRATION:
Four female mice were treated with different concentrations of the test item and vehicle alone by topical application at the dorsum of each ear lobe (left and right) on three consecutive days. Five days after the first topical application, the mice were intravenously injected into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Five hours after intravenous injection, the mice were sacrificed and the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a ß-scintillation counter.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
-

Results and discussion

Positive control results:
EC3 = 6.7 % (w/v)

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Test item Calculation Result concentration (%) / S.I. Control Group / --- 5 / 1.6 10 / 1.8 25 / 2.8
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Test item Calculation Result concentration (%) / DPM per lymph node Control Group / 305.2 5 / 500.7 10 / 540.3 25 / 857.8

Any other information on results incl. tables

Test item concentration [% (w/v)]

Group

Measurement DPM

Calculation

Result

DPM-BGa)

Number of lymph nodes

DPM per lymph nodeb)

S.I.

-

BG I

16

-

-

-

-

-

BG II

19

-

-

-

-

-

1

2459

2442

8

305.2

 

5

2

4023

4006

8

500.7

1.6

10

3

4340

4323

8

540.3

1.8

25

4

6880

6863

8

857.8

2.8

BG      = Background (1 ml 5 % trichloroacetic acid) in duplicate

1         = Control Group

2-4      = Test Group

S.I.      = Stimulation Index

a)        = The mean value was taken from the figures BG I and BG II

b)        = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by

             dividing the measured value by the number of lymph nodes pooled

 

The EC3 value could not be calculated, since all S.I.’s are below 3.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test item Naptolon-Na TF was found to be not a skin sensitiser in the LLNA when tested at up to 25 % in DMF.
Executive summary:

In the study the test item suspended in 25 % DMF was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay according to OECD guideline No. 429 was performed using test item concentrations of 5, 10, 25 %. The animals 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 1.6, 1.8, and 2.8 were determined. The test item was found to be not a skin sensitiser in this assay.