14H-anthra[2,1,9-mna]thioxanthen-14-one

Endpoint summary

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:

weight of evidence

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Current Guideline study according to GLP

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; B.V. Postbus 6174; NL - 5960 AD Horst / The Netherlands
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 20,2 +/- 1,2 g
- Housing: individual
- Diet (e.g. ad libitum): ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

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

Remarks:

in a repeat experiment: propylene glycol

Concentration:

0-5-10-25 %

No. of animals per dose:

4

Details on study design:

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: Si >/= 3 and positie dose/response relation

TREATMENT PREPARATION AND ADMINISTRATION:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 5, 10 and 25% (w/v) in acetone:olive oil, 4:1 (v/v) in the main experiment, and 25% (w/v) in propylene glycol in the repeat experiment. The application volume, 25 μl, was spread over the entire dorsal surface (∅ ∼ 8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals). A hair dryer was used to dry the ear's surface as quickly as possible to avoid loss of test item applied.

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Tables below

Table 1 Result from Experiment 1

 

Group/Test item conc. (%)	DPM	DPM - Background	Number of LN	DPM per LN	Stimulation Index (SI)
Back ground 1	0
Back ground 2	2,4
Aceton/Olive oil	3059,2	3058	8	382,3	1
5%	14134	14130	8	1766,6	4,6
10	13366	13365	8	1670,6	4,4
25	11291	11289	8	1411,2	3,7

 

 

Table 1 Result from Experiment 2

 

Group/Test item conc. (%)	DPM	DPM - Background	Number of LN	DPM per LN	Stimulation Index (SI)
Back ground 1	34,5
Back ground 2	34,1
Propylene glycol	2360,5	2326,2	8	290,8	1
25	9412,3	9378	8	1172,3	4,0

 

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

As the stimulation index was above 3 in all tested concentrations the test material is regarded as a sensitiser under the conditions of the LLNA.

Executive summary:

In the study the test item dissolved in acetone:olive oil, 4:1 (v/v) in the main experiment and in propylene glycol in the repeat experiment was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay was performed using test item concentrations of 5, 10 and 25% in the main experiment and 25% in the repeat experiment.

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 4.6, 4.4 and 3.7 were determined with the test item at concentrations of 5, 10 and 25% (w/v) in acetone:olive oil, 4:1 (v/v), respectively.

In the repeat experiment a Stimulation Index of 4.0 was determined with the test item at a concentration of 25% (w/v) in propylene glycol.

An EC3 value could not be calculated since the S.I. was above 3 even at the lowest tested concentration of 5 % (w/v).

The test item was found to be a skin sensitiser under the described conditions.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The test material, though not sensitising itself, is considered a skin sensitiser due to the presence of sensitising impurites. Purification to prevent sensitisation is possible only on a laboratory scale but not in large scale production. The limit concentration of impurites is considered at 0.5% (w/w)

Migrated from Short description of key information:
The test matrial did induce skin sensitisation in the LLNA in mice in several studies depending on the degree of impurities present. Purified samples (>99%) did not induce skin sensitisation.

Justification for selection of skin sensitisation endpoint:
Most recent study, representative result

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Due to the sensitising potential of impurities from the production process the material should be classified and labelled if the level of impurities exceeds 0.5 % (w/w).