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Toxicological information

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 Apr 1997 - 06 Jun 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Physical state: white powder
- Analytical purity: 99.2%
- Lot/batch No.: 212/02/96
- Expiration date of the lot/batch: 1998-02-12
- Stability under test conditions: substance is stable at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Biocon Research, Pretoria, South Africa
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: pre-test (male): 434 - 532 g; main test (female): 302 - 503 g
- Housing: conventionally, 5 animals per cage (standard fibre glass)
- Diet: food ad libitum, supplemented with lettuce leaves once weekly
- Water: water ad libitum, supplemeted with Vitamin C
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 21
- Humidity (%): 43 - 70
- Air changes (per hr): approx. 15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours cycle

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
a) first induction intradermally: 10% solution in physiological saline
b) second induction epicutaneously: 50% solution in physiological saline
c) for challenge epicutaneously: 50% solution in physiological saline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
a) first induction intradermally: 10% solution in physiological saline
b) second induction epicutaneously: 50% solution in physiological saline
c) for challenge epicutaneously: 50% solution in physiological saline
No. of animals per dose:
test group: 20
pre-test: 6
Details on study design:
RANGE FINDING TESTS:
Dermal irritations (erythema/oedema) were investigated using different concentrations.
A 10 % solution of Diuron in saline, as the highest dose not causing local necrosis, ulceration or systemic toxicity was selected for intradermal
induction. For topical induction, a 50 % solution was selected, the highest concentration that did not produce irritation.
The maximum non-irritant concentration for challenge was 50 % Diuron in saline.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Test groups:
Day 0: Three pairs of injections (2 x 0.1 mL):
Freund’s complete adjuvant with physiological saline (50:50) and the test substance (10% in physiological saline)
close to the first two injections, both close to the head
the test substance (10%) in a mixture Freund’s complete adjuvant with physiological saline (50:50), towards the caudal part of the test area.
Day 7: epicutaneous administration of the test article. The test substance was held in contact with the skin under an occlusive patch for 48 hours.
- Control group: The control group was treated similarly, receiving vehicle only.
- Site: scapular region, 4 x 6 cm2
- Concentrations: 10% test substance in saline and 50% test substance in petrolatum,
0.1% Freund’s complete adjuvant in an equal volume physiological saline

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: The test substance was held in contact with the skin under an occlusive patch for 24 hours and was removed with sterile water
afterwards
- Site: flanks
- Concentrations: 50% in physiological saline (maximum non-irritant concentration)
- Evaluation (hr after challenge): 48h and 72h after challenge

OTHER:
- Clinical signs and body weights were recorded.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Results of the test study:

All guinea-pigs survived the study. Body weights were comparable between the two groups.

No erythema or oedema was observed in any of the animals challenged with Diuron.

It is concluded that the test item did not provoke skin sensitization at a 50% concentration in guinea pigs.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:

A reliable GPMT test was conducted in compliance with OECD Guideline 406. Female guinea-pigs were intradermally and epicutaneously induced before being challenged with a 50% Diuron solution in saline. No skin reaction on the basis of erythema and oedema (sensitization rate 0%) was observed. A 50% solution of Diuron did not provoke skin sensitization (Sharp 1997).