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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Jan - 09 Mar 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
- Principle of test: guinea pig maximisation test with subsequent modified Buehler test (epicutaneous test)
- Short description of test conditions: first control group of maximisation test was used as test group in subsequent epicutaneous test (with additional untreated animals as control)
- Parameters analysed / observed: skin reaction
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study predates LLNA method

Test material

Constituent 1
Chemical structure
Reference substance name:
7-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-4-hydroxy-3-[(4-methoxy-2-sulphophenyl)azo]naphthalene-2-sulphonic acid, sodium salt
EC Number:
286-839-5
EC Name:
7-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-4-hydroxy-3-[(4-methoxy-2-sulphophenyl)azo]naphthalene-2-sulphonic acid, sodium salt
Cas Number:
85391-83-9
Molecular formula:
C21H14ClF2N5O8S2.xNa
IUPAC Name:
7-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-4-hydroxy-3-[(4-methoxy-2-sulphophenyl)azo]naphthalene-2-sulphonic acid, sodium salt
Test material form:
solid: particulate/powder
Details on test material:
Reactive Red 123

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Remarks:
Bor:DHPW
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: 5 to 7 weeks
- Weight at study initiation: mean 325g, range 288 - 375g
- Housing: 5 animals in one makrolon cage (Type IV)
- Diet (e.g. ad libitum): Altromin 3020, ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): ca. 50%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12h/12h

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
First induction: 2 x 3 injections: ca 0.1 mL each
1. Freund's complete adjuvant in physilogical saline (cranial)
2. 5% test item in physilogical saline (medial)
3. 5% test item in solution of physilogical saline and Freund's complete adjuvant (caudal)
control: same treatment without test item
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
Second induction: 5 mL of physiological saline with 12% test item on a patch, covered with aluminium foil for 48h
control: same treatment without test item
Day(s)/duration:
Day 8 for 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
Bühler Test: subsequent epicutaneous test with first control group of maximisation test: 12%
1. induction: 1 challenge from maximisation test: 5 mL for 24 h
2. and 3 induction: 5 mL on a patch for 6 h
7 days between the inductions
Day(s)/duration:
Day 22 of GPMT = Day 1 Bühler Test for 24 h; Day 8 and 22 Bühler Test for 6 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
0.5mL of physiological saline with 12% test item on a patch
Day(s)/duration:
Day 22 for 24h
Adequacy of challenge:
other: concentration proved to be irritating in challenge
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
0.5 mL of physiological saline with 6 % test item on a patch
Day(s)/duration:
Day 29 for 24 h
Adequacy of challenge:
highest non-irritant concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
Bühler Test: 6% and 9% at 0.5 mL
Day(s)/duration:
Day 36 for 6 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
maximisation test: 20 per dose, 10 per control
epicutaneous test: 10 per dose, 10 per control
Details on study design:
MAXIMISATION TEST
A. INDUCTION EXPOSURE
- No. of exposures: two (one intradermal, one epicutaneous)
- Exposure period: epicutaneous induction one week after intradermal induction
- Site: intradermal injections each one cranial, medial and caudal; epicutaneous induction on skin area of injections
- Concentrations: intradermal injections with 0.1mL physilogical saline with 5% test iteml; epicutaneous induction with 0.5mL of physiological saline with 12% test item on a patch

B. CHALLENGE EXPOSURE
- No. of exposures: two
- Day(s) of challenge: 3 and 4 weeks after intradermal induction
- Exposure period: 24h
- Site: left
- Concentrations: first challenge: 12%; second challenge: 6%
- Evaluation (hr after challenge): 48 and 72h after application

EPICUTANEOUS TEST
A. INDUCTION EXPOSURE
- No. of exposures: three (epicutaneous)
- Exposure period: epicutaneous inductions in interval of one week
- Exposure period: first: 24h, second and third: 6h
- Site: left
- Concentrations: 0.5mL of physiological saline with 12% test item on a patch

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: 2 weeks after last induction
- Exposure period: 6h
- Site: left
- Concentrations: 6 and 9% test item
- Evaluation (h after challenge): 24, 48 and 72h after application
Positive control substance(s):
not specified

Results and discussion

Positive control results:
N/A

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
12%
No. with + reactions:
15
Total no. in group:
20
Remarks on result:
not determinable
Remarks:
irritating effects
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
12%
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
not determinable
Remarks:
irritating effects
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
12%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: irritating effects
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
12%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: irritating effects
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
6%
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
6%
No. with + reactions:
5
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
6%
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
6%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
9% - Bühler Test
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
9% - Bühler Test
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
9% - Bühler Test
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The test item was found to have skin sensitising properties in the GPMT and in the Buehler test. The substance is classifiable according to CLP criteria.

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