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Diss Factsheets

Administrative data

Description of key information

Guinea pig. Not sensitising. OECD 406, OPP 81-6, EU Method B.6, JMAFF 59-NohSan-4200; Reliability = 1

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF Japan, 59 NohSan No. 4200
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Not specified in the report
Specific details on test material used for the study:
Substance ID: DPX-JE874-221 Technical
Lot #: DPX-JE874-221
Purity: 97.4%
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson Mill Farm, Jamesburg, New Jersey
- Weight at study initiation: 352 to 475 g
- Housing: One/cage (Stainless steel with elevated wire mesh flooring)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.4-21.9°C
- Humidity: 39-67%
- Photoperiod: 12 hour light/dark cycle
Route:
other: intradermal and topical
Vehicle:
other: white mineral oil
Concentration / amount:
Group I (test article group)
20 animals received six injections (0.05 mL each).
1. Freund's Complete Adjuvant emulsified in deionized water (1:1)
2. 5% v/v dilution of H-20324 in white mineral oil
3. 5% v/v dilution of H-20324 in white mineral oil emulsified with Freund's Complete Adjuvant (1:1)
On Day 8, a 20 mm X 45 mm patch with 0.8 g (0.4 g test article mixed with 0.4 g of white mineral oil) was applied to the intradermal injection area.
Day(s)/duration:
Day 1 (intradermal) and 8 (topical)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
other: intradermal and topical
Vehicle:
other: white mineral oil
Concentration / amount:
Group II (test article vehicle control group)
20 animals received six injections (0.05 mL each).
1. Freund’s Complete Adjuvant emulsified in deionized water (1:1)
2. Vehicle Control (white mineral oil) sample alone
3. Vehicle Control (white mineral oil) sample emulsified with Freund’s Complete Adjuvant (1:1)
On Day 8, a 20 mm X 45 mm patch soaked with 0.4 mL white mineral oil was applied to the intradermal injection area.
Day(s)/duration:
Day 1 (intradermal) and 8 (topical)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
other: intradermal and topical
Vehicle:
other: 50% ethanol:saline
Concentration / amount:
Group III (Positive control group - DNCB)
6 animals received six injections (0.05 mL each).
1. Freund's Complete Adjuvant emulsified in deionized water (1:1)
2. 0.10% DNCB in 50% ethanol in saline
3. 0.10% DNCB in 50% ethanol: saline emulsified in Freund’s Complete Adjuvant (1:1)
On Day 8, a 20 mm X 45 mm patch soaked with 0.4 mL of 0.10% DNCB in 50% ethanol:saline was applied to the intradermal injection area.
Day(s)/duration:
Day 1 (intradermal) and 8 (topical)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
other: intradermal and topical
Vehicle:
other: 50% ethanol:saline
Concentration / amount:
Group IV (Positive control vehicle group)
6 animals received six injections (0.05 mL each).
1. Freund's Complete Adjuvant emulsified in deionized water (1:1)
2. 50% ethanol in saline
3. 50% ethanol: saline emulsified in Freund’s Complete Adjuvant (1:1)
On Day 8, a 20 mm X 45 mm patch soaked with 0.4 mL of 50% ethanol was applied to the intradermal injection area.
Day(s)/duration:
Day 1 (intradermal) and 8 (topical)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: white mineral oil
Concentration / amount:
The 100% level was prepared by mixing equal weights of test article and white mineral oil and applying an amount (0.2 g) containing 0.1 g of test article (100% of dose) to the chamber which was positioned on the left anterior flank. The second level, 0.1 g of a 33% w/w dilution in white mineral oil (1/3 of the challenge dose amount) was applied to a second chamber and positioned on the left posterior flank.
Day(s)/duration:
Day 22 (Group I and II)
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
One chamber, soaked with 0.1 mL of acetone, was positioned on the right flank. The remaining two chambers were soaked with 0.1 mL of 0.10% DNCB in acetone and 0.03% DNCB in acetone and were positioned on the left flank, anterior and posterior, respectively.
Day(s)/duration:
Day 22 (group III and IV)
Adequacy of challenge:
not specified
No. of animals per dose:
Group I: 20 males
Group II: 20 males
Group III: 6 males
Group IV: 6 males
Details on study design:
RANGE FINDING TESTS:
Irritation screens: The first set of three animals received six injections (0.05 mL each) to each animal, three of these were concentrations of 1, 3 and 5% of the test article in acetone and three concentrations were of the same concentrations in a 1:1 emulsion of Freund's Complete Adjuvant, Since these screens (acetone) were corrosive, additional screens were performed on the second set of three animals, using white mineral oil as the vehicle. The 5% level in white mineral oil appeared to be well-tolerated and was chosen for the main study.
Levels of 100% (0.1 g mixed with 0.1 g of white mineral oil) and 50% (0.05 g mixed with 0.05 g of white mineral oil) were screened to determine the irritation potential of the test article. No skin irritation was noted for either of the 2 test article levels or the vehicle. The 100% level (premixed) was chosen for the challenge phase of this study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One intradermal injection and a topical application
- Exposure period: 48 h for topical application
- Test groups: Group I (test article group) & Group II (test article vehicle control group)
- Control group: Group III (Positive control group - DNCB) & Group IV (Positive control vehicle group)

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day of challenge: Day 22
- Exposure period: 24 h
- Test groups: Group I (test article group) & Group II (test article vehicle control group)
- Control group: Group III (Positive control group - DNCB) & Group IV (Positive control vehicle group)
Challenge controls:
The 100% level was prepared by mixing equal weights of test article and white mineral oil and applying an amount (0.2 g) containing 0.1 g of test article (100% of dose) to the chamber which was positioned on the left anterior flank. The second level, 0.1 g of a 33% w/w dilution in white mineral oil (1/3 of the challenge dose amount) was applied to a second chamber and positioned on the left posterior flank.
Positive control substance(s):
yes
Remarks:
1-chloro-2, 4-dinitrobenzene (DNCB)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 and 0.03% in acetone
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
Body weight loss was observed in one animal between day 21 and 25.
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1 and 0.03% in acetone
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
Body weight loss was observed in one animal between day 21 and 25.
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 and 33% w/w in white mineral oil
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Body weight loss was observed in one animal between day 7 and 14 and in one animal between day 14 and 21.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 and 33% w/w in white mineral oil
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Body weight loss was observed in one animal between day 7 and 14 and in one animal between day 14 and 21.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 and 33% w/w in white mineral oil
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
One animal was found dead but not related to test article administration. Body weight loss was observed in three animals between day 7 and 14 and in three animals between day 21 and 25.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 and 33% w/w in white mineral oil
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
One animal was found dead but not related to test article administration. Body weight loss was observed in three animals between day 7 and 14 and in three animals between day 21 and 25.
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance did not produce delayed contact hypersensitivity in guinea pigs.
Executive summary:

The purpose of this study was to determine the potential of the test substance to cause delayed contact hypersensitivity in guinea pigs according to the guidelines OECD 406 and US EPA 81-6. The test substance was moistened with white mineral oil and tested on the clipped, intact skin of male guinea pigs.  1-Chloro-2,4-dinitrobenzene (DNCB) was used to demonstrate the ability of the test system to detect a skin sensitizer (positive control group). A group of male guinea pigs was treated with white mineral oil (vehicle) at induction, and the test substance and white mineral oil at challenge (vehicle control group). In addition, a group of male guinea pigs treated with DNCB at challenge (naive positive control group).


No dermal irritation was observed 24, or 48 hours post-challenge for the test article and vehicle groups at either test article concentration site (100% or 33%) or at the vehicle control site.


The positive control animals exhibited moderate redness at 24 hours after the challenge application and scattered mild redness to moderate redness at 48 hours at the test site challenged with a 0.1% concentration of DNCB. Barely perceptible redness to moderate redness was exhibited in these animals at the 0.03% concentration of DNCB at 24 and 48 hours after the challenge application. No redness was observed 24 or 48 hours after the challenge application of the vehicle (acetone).


No redness was observed at 24, or 48 hours post-challenge for the positive control vehicle animals at the 0.1% and 0.03% concentration of DNCB. No irritation was exhibited by the vehicle (acetone) at 24, or 48 hours post-challenge for these animals.


Under the conditions of this study, the test substance did not produce delayed contact hypersensitivity in guinea pigs.


On the basis of the nature of effects observed in this study and according to the guide for the labeling of dangerous substances published in the Official Journal of the European Communities (EEC Directive 91/325), the test substance is not a skin sensitizer.

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

The dermal sensitization potential of the test substance was evaluated in guinea pigs by the Magnusson and Kligman maximisation method in male Hartley guinea pigs. No dermal irritation was observed 24, or 48 hours post-challenge for the test article and vehicle groups at either test article concentration site (100% or 33%) or at the vehicle control site. Under the conditions of this study, the test substance did not possess skin sensitising potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

There was no evidence of dermal sensitisation in guinea pigs. The substance does not need to be classified for skin sensitisation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.