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Diss Factsheets

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:
March 31- May 6, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data on reliability check of the test
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data on reliability check of the test
Qualifier:
according to guideline
Guideline:
other: US EPA FIFRA Pesticide Assessment Guidelines (1984)
Deviations:
not specified
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Murine Local Lymph Node Assay (LLNA) is the first-choice method for in vivo testing according to the REACH Regulation. However, this reliable guinea pig maximisation test was performed before entry into force of the REACH Regulation.

Test material

Constituent 1
Chemical structure
Reference substance name:
Hydroxyl-2-pyridone
EC Number:
212-506-0
EC Name:
Hydroxyl-2-pyridone
Cas Number:
822-89-9
Molecular formula:
C5H5NO2
IUPAC Name:
1-hydroxy-1,2-dihydropyridin-2-one
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study reports): Oxy PYRION
- Physical state: solid (powder)
- Appearance: white speckled gold powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 93100020

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At ambient temperature in a glass jar
- Stability under test conditions: Stable

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: David Hall, Darley Oaks, Newchurch, Burton on Trent, Staffordshire, England
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 361-442 g for controls, 359-438 g for test animals
- Housing: Stainless steel cages with grid floors and tops, suspended in mobile racks. 5 same sex animals per cage.
- Diet (e.g. ad libitum): Commercially available pelleted guinea pig diet, ad libitum
- Water (e.g. ad libitum): Public tap water, ad libitum
- Acclimation period: at least 6 but not more than 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 °C (15-23 °C)
- Humidity (%): 55% (40-70% range)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 dark/12 light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
5% w/v oxypyrion in propylene glycol/0.1 mL
Day(s)/duration:
Day 1
Adequacy of induction:
highest technically applicable concentration used
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
5% w/v oxypyrion in propylene glycol in FCA/0.1 mL
Day(s)/duration:
Day 1
Adequacy of induction:
highest technically applicable concentration used
Route:
intradermal
Vehicle:
other: Purified water
Concentration / amount:
FCA 1:1 mixture of the adjuvant concentrate with purified water/0.1 mL
Day(s)/duration:
Day 1
Adequacy of induction:
other: according to OECD Guideline 406
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
50% w/v oxypyrion in propylene glycol/0.6 mL
Day(s)/duration:
Day 8/48 hours (secondary induction)
Adequacy of induction:
other: was to cause at most, a weak or moderate inflammatory response and the concentration used at challenge was to be at the highest sub-irritant level; maximum practicable concentration of the test material and three lower concentrations in vehicle
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
10% w/v oxypyrion in propylene glycol/0.03 mL
Day(s)/duration:
Day 22/24 hours
Adequacy of challenge:
highest non-irritant concentration
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
3% w/v oxypyrion in propylene glycol/0.03 mL
Day(s)/duration:
Day 22/24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Screening test: 4 animals
Main test: The test group consisted of twenty animals and the control group ten animals, evenly divided by sex.
Details on study design:
RANGE FINDING TESTS:
The study design included a primary skin irritation screen which imposed limits on the concentration of the test material used during the main study.
Pre-treatment formulation trials indicated that 10% w/v oxypyrion in propylene glycol was the maximum concentration that would pass through a hypodermic needle. The maximum practicable concentration of the test material in the chosen vehicle was taken as 50% w/v for topical administration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 pairs of injections per animal, anterior-FCA; middle-test substance in propylene glycol; posterior-test substance in propylene glycol in FCA
- Exposure period: Day 1 injection
- Test groups: 20 animals
- Control group: 10 animals
- Site: primary induction: dorsal median line; secondary induction: dermal site overlying the scapulae
- Frequency of applications: Once
- Duration: primary induction: single injection; secondary induction: 48 hours
- Concentrations: primary induction: 5% w/v oxypyrion in propylene glycol or 5% w/v oxypyrion in propoylene glycol in FCA; secondary induction: 50% w/v oxypyrion in propylene glycol

B. CHALLENGE EXPOSURE
- No. of exposures: 1 per animal and vehicle
- Day(s) of challenge: Day 22
- Exposure period: 1 h
- Test groups: 20 animals
- Control group: 10 animals
- Site: Both flanks of animals, left side-0.03 mL vehicle, right side-0.03 mL of 2 concentrations of test substance, occluded
- Concentrations: 3% and 10%
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Controls were untreated sites on the left flank of each challenged animal.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
propylene glycol
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
propylene glycol
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Propylene glycol
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
propylene glycol
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10% w/v oxypyrion in propylene glycol
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
eschar formation in one animal and slight erythema in one test animal
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10% w/v oxypyrion in propylene glycol
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
eschar formation in one animal and slight erythema in one animal
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% w/v oxypyrion in propylene glycol
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
slight erythema in 2 control animals
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10% w/v oxypyrion in propylene glycol
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3% w/v oxypyrion in propylene glycol
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3% w/v oxypyrion in propylene glycol
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
3% w/v oxypyrion in propylene glycol
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
3% w/v oxypyrion in propylene glycol
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
other: all groups
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Induction:

Intradermal injection of 5% w/v oxypyrion in propylene glycol, alone or in Freund's Complete Adjuvant caused slight or moderate erythema, eschar formation and pallor, and a low incidence of discoloration.

Occluded topical application of 50% w/v oxypyrion in propylene glycol gave rise to slight erythema, eschar formation, and a single case of oedema and exfoliation.

Challenge:

Application of 10% w/v oxypyrion in propylene glycol caused eschar formation in 1 test animal, and slight erythema in 1 test and 2 control animals. Barely perceptible erythema was observed in 3 test animals and 1 control animal.

Application of 3% w/v oxypyrion in propylene glycol caused barely perceptible erythema in 1 test and 1 control animal.

Application of propylene glycol alone gave rise to a single case of barely perceptible erythema amongst the test animals, as the only reaction to treatment.

General health and bodyweight:

The animals remained in overt good health and achieved anticipated overall body weight gains. On day 25, the body weight range of the control animals was 521 -726 g and of the test animals 522 -652 g.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The incidence of response was below the EEC limit value (30%) to classify the test material as a dermal sensitizer. It is concluded that under the conditions of the study, repeated application of the test substance did not cause delayed contact hypersensitivity in the guinea pig.