Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 November 2015 - 11 December 2015
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 guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The LLNA is the study of choice for skin sensitisation. As detailed in the OECD 429 guideline, despite the advantages of the LLNA, it should be recognised that there are certain limitations that may necessitate the use of TG 406. Chemical groups such as metal salts, organometal, unsaturated compounds and surfactants have been known to be linked to false positive. The Substance is considered to be amphiphilic and therefore would likely have surfactant characteristics, and an unsaturated compound which are known to be falsely positive in the LLNA. Therefore a Guinea Pig Study, OECD 406, was conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
Physical Description: Pale amber waxy solid
Purity: 100%
Storage Conditions: Kept in a controlled room temperature area

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Temperatures of 68°F to 72°F (20°C to 22°C) with a relative humidity of 45% to 55% were maintained. A 12 hour light/12 hour dark cycle was maintained, except when interrupted for designated procedures. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
Moistened with corn oil
Concentration / amount:
100% (0.3 mL)
Day(s)/duration:
3 inductions (Day 0, 7, 14) over 3 weeks / 6 hour exposure per induction
Adequacy of induction:
highest technically applicable concentration used
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
75%/ 0.3 mL
Day(s)/duration:
1 Challlenge (Day 28)/ 6 hour exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 animals for the main test
10 animals for control
Details on study design:
The dermal sensitization potential of the Substance was evaluated in Hartley-derived albino guinea pigs. Ten male and 10 female guinea pigs were topically treated with the Substance, as received, once per week, for 3 consecutive weeks. Following a 2-week rest period, a challenge was performed whereby the 20 test and 10 previously untreated (naïve) challenge control guinea pigs were topically treated with 75% the Substance in PEG 400.
Challenge controls:
On the day prior to challenge dose administration, the test, HCA test, challenge control, and HCA challenge control animals were weighed and the hair was removed from the right side of the animals. On the day following clipping (Day 28), Hilltop chambers were applied.
Positive control substance(s):
yes
Remarks:
a-Hexylcinnamaldehyde (HCA)

Results and discussion

Positive control results:
The results of the HCA positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitizers.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
No related clinical signs were noted during the study
Remarks on result:
positive indication of skin sensitisation
Remarks:
scores of 1 or 2
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
No related clinical signs were noted during the study
Remarks on result:
positive indication of skin sensitisation
Remarks:
score of 1 or 2
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
No related clinical signs were noted during the study
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No related clinical signs were noted during the study
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2.5%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
2.5%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

See attached background documents

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Based on the results of this study,the Substance s considered to be a contact sensitizer in guinea pigs as >15% of the test animals responded at challenge.
Executive summary:

The dermal sensitization potential ofthe Substance was evaluated in Hartley-derived albino guinea pigs. Ten male and 10 female guinea pigs were topically treated withthe Substance, as received,once per week, for 3 consecutive weeks. Following a 2-week rest period, a challenge was performed whereby the 20 test and 10 previously untreated (naïve) challenge control guinea pigs were topically treated with 75%the Substancein PEG 400.

 

Following challenge with 75%the Substancein PEG 400, dermal scores of 1 or 2 were noted in 19/20 test animalsand1/10 challenge control animals at the 24-hour scoring interval. At the
48-hour scoring interval, dermal scores of 1 or 2 were noted in 20/20 test animals. Dermal reactions in the remaining test and challenge control animals were scores of 0 or ±. Group mean dermal scores were higher in the test animals (1.6) as compared to challenge control animals (0.3 to 0.2).

 

Based on the results of this study,the substanceis considered to be a contact sensitizer in guinea pigsas >15% of the test animals responded at challenge. The results of the HCA positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitizers.