Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
16 January to 19 February 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study. The test substance is leukoindigo, the reduced form of the registered substance indigo. The leucoindigo is precipitated by neutralising of the alkaline leucoindigo solution with CO2 and mixed with molasses to prevent the leucoindigo from oxidation to indigo (CAS number 482-89-3 )
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., Burton-on-Trent, UK
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 292 to 379 g
- Housing: 4/cage
- Diet: guinea pig FD1 diet, Special Diet Services Ltd., Essex, UK ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 45-55
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 16 January to 19 February 1987
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: 0.5%
Epicutaneous induction: undiluted as supplied
Epicutaneous challenge: 25%
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: 0.5%
Epicutaneous induction: undiluted as supplied
Epicutaneous challenge: 25%
No. of animals per dose:
Control group: 10
Dose group: 20
Details on study design:
RANGE FINDING TESTS:
up tp 2 dose levels for each application were tested in each 1 or 2 guinea pigs

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal, 1 dermal
- Exposure period: occlusive dressing: 48 hours
- Test groups: TS in distilled water/FCA or undiluted
- Control group: distilled water/FCA
- Site: shoulder
- Frequency of applications: single
- Intradermal injections: 2 x 3 preparations: 50% FCA, 0.5% TS in distilled water, 0.5% TS in 50% FCA - treatment group
50% FCA, distilled water, 50% FCA - control group
- Dermal application: 0.2-0.3 mL undiluted TS (40x20 mm patch) occlusive for 48 hour

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 hours
- Test groups: TS + water
- Control group: TS + water
- Site: right flank: TS; left flank: water
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48 hours

SCORING:
0 - no reaction
1 - scattered mild redness
2 - moderate and diffuse redness
3 - intense redness and swelling

EVALUATION of RESPONSE:

0% - non-sensitizer
> 0-8% - weak sensitizer
>8-28% - mild sensitizer
>28-64% - moderate sensitizer
>64-80% - strong sensitizer
>80-100% - extreme sensitizer
Challenge controls:
intraindividual in TS and control animals
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
5
Total no. in group:
19
Clinical observations:
blue staining of skin/hair not preventing erythema assessment
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 5.0. Total no. in groups: 19.0. Clinical observations: blue staining of skin/hair not preventing erythema assessment.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
4
Total no. in group:
19
Clinical observations:
blue staining of skin/hair not preventing erythema assessment
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 4.0. Total no. in groups: 19.0. Clinical observations: blue staining of skin/hair not preventing erythema assessment.
Reading:
other: 1st and 2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
blue staining of skin/hair not preventing erythema assessment
Remarks on result:
other: Reading:
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Positive skin reactions were found in 5 animals ( 4 x score 1, 1 x score 2) at the 24-hour and in 4 animals (4 x score 1) at the 48-hour assessment.

According to the evaluation system used in this study, the test item was classified as "mild sensitizer". According to the EU evaluation system the test item has no sensitizing properties.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There is guinea pig data for a 50% leucoindigo preparation. Positive skin reactions were found in 5 animals ( 4 x score 1, 1 x score 2) at the 24-hour and in 4 animals (4 x score 1) at the 48-hour assessment. According to the evaluation system used in this study, the test item was classified as "mild sensitizer". According to the EU evaluation system the test item has no sensitizing properties

The leucoindigo rapidly oxidizes to indigo under testing conditions, which can be noticed by the blue staining of the animals' skin. Furthermore, human data from literature using Indigo dispersible powder as test substance confirmed the negative test result. In addition, there is several hundred years of experience with the usage of indigo, and no sensitizing effect during this usage is reported.


Migrated from Short description of key information:
No skin-sensitizing properties

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Based on the negative skin sensitization test, no respiratory sensitization is expected. In addition, the acute inhalation studies with Indigo in rats exposed to a saturated atmosphere for up to 8 hours did not lead to any adverse effects.


Migrated from Short description of key information:
No respiratory-sensitizing properties

Justification for classification or non-classification

No sensitizing effects observed in animal and human studies