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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Magnusson and Kligman method
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF 12-Nousan-8147 (2000)
Deviations:
no
GLP compliance:
yes
Type of study:
other: Magnusson and Kligman (M&K) Method

Test material

1
Chemical structure
Reference substance name:
8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid
Cas Number:
353258-35-2
Molecular formula:
C9H4ClF3N2O2
IUPAC Name:
8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid
Specific details on test material used for the study:
Test substance: IN-QEK31-011
Lot number: SG0312574
Purity: 98.2%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
1% w/w
Day(s)/duration:
on Day 01
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
other: Topical
Vehicle:
propylene glycol
Concentration / amount:
45% w/w
Day(s)/duration:
on Day 07 (48 hour application)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
The HNIC (the highest concentration that produced responses in four guinea pigs no more severe than two scores of 0.5 and two scores of zero) selected for the challenge phase was a 60% w/w mixture in propylene glycol. A quantity equal to 0.5 mL of propylene glycol was applied to one chamber and positioned on the right middle flank. The remaining two chambers containing 0.5 grams of a 60% w/w mixture of the test substance in propylene glycol (HNIC) and 0.5 mL of a 20% w/w mixture in propylene glycol (33% dilution of the HNIC) were positioned on the left front and rear flank, respectively.
Day(s)/duration:
on Day 20 (24 hour application)
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Preliminary Irritation Testing: 12 (4/group)
Test Group: 20
Test Vehicle Control Group: 10
Positive control substance(s):
no
Remarks:
alpha-Hexylcinnamaldehyde

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20 and 60% w/w mixture in propylene glycol and 100% vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20 and 60% w/w mixture in propylene glycol and 100% vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20 and 60% w/w mixture in propylene glycol and 100% vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20 and 60% w/w mixture in propylene glycol and 100% vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is not considered to be a contact skin sensitizer.
Executive summary:

A Magnusson-Kligman test was conducted with guinea pigs to determine the potential for test substance to invoke dermal skin sensitization reactions according to guidelines OECD 406, US EPA OPPTS 870.2600, EC B.6, JMAFF. The study was conducted using four stages; preliminary irritation screens, a two-stage induction phase, and a challenge phase as described below.


Preliminary irritation testing was performed on twelve animals to determine appropriate concentrations of the test substance that could be used for both intradermal and topical induction as well as topical challenge.


An emulsion of 50% v/v Freund’s Adjuvant Complete in distilled water was used during the intradermal injection screening and the injection induction phases. This emulsion was thoroughly mixed using a stir plate and is referred to throughout the report as an emulsion of Freund’s Adjuvant Complete.


The first induction phase involved six intradermal injections into the suprascapular area of each of 20 guinea pigs. These doses were comprised of pairs of injections of the test substance in propylene glycol (1% w/w), the test substance (1% w/w) combined with an emulsion of Freund’s Adjuvant Complete, as well as an emulsion of Freund’s Adjuvant Complete alone. A sham control group (ten animals) was maintained under the same environmental conditions and received injections of propylene glycol (100%), propylene glycol (50% w/w) combined with an emulsion of Freund’s Adjuvant Complete, as well as an emulsion of Freund’s Adjuvant Complete alone. Approximately 24 and 48 hours after the injections, all sites were evaluated for an irritation response (erythema).


Approximately one week later, the second phase of induction was conducted. The test substance as a 45% w/w mix in propylene glycol (test group) or propylene glycol (test vehicle control group) was applied topically for a period of 48 hours to the area encompassing the intradermal injection sites. Approximately one hour after the topical induction patches were removed, all animals were scored for erythema. Approximately two weeks later, a primary challenge consisting of three occluded applications was conducted on each animal. One Hill Top Chamber containing 0.5 mL of propylene glycol was applied to a naive site on the right middle flank of each animal. The remaining two Hill Top Chambers containing 0.5 grams of the HNIC (Highest Non-Irritating Concentration, determined in the preliminary irritation screen to be an 60% w/w mixture in propylene glycol) of the test substance and 0.5 mL of a 33% dilution of the HNIC (20% w/w mixture in propylene glycol) were positioned on two naive sites on the left front and rear flank, respectively, for approximately 24 hours. The test vehicle control group was also treated with the test substance and test vehicle (as described above) at challenge. Approximately 24 and 48 hours after challenge patch removal, all animals were scored for a sensitization response (erythema).


Based on the results of this study, test substance is not considered to be a contact skin sensitizer. The positive response observed in the historical positive control validation study with alpha-Hexylcinnamaldehyde, ≥ 95% (HCA) validates the test system used in this study.