Registration Dossier

Administrative data

Description of key information

Based physical chemical characteristics of the Substance there is high uncertainty regarding the applicability to the current in vitro studies, therefore the predictions are unlikely to be meaningful and/or represent the true hazard of the Substance. In conclusion it was considered appropriate to conduct an in vivo study approach to minimise the uncertainty for this Substance.

The Substance is considered to be amphiphilic and therefore would likely have surfactant characteristics,and is a unsaturated substance, which are known to be falsely positive in the LLNA. Therefore a Guinea Pig Study, OECD 406, was conducted.

Based on the results of the OECD 406 study, the Substance s considered to be a contact sensitizer in guinea pigs as >15% of the test animals responded at challenge.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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
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.
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
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.
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
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)
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.
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

See attached background documents

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.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
The current in vitro studies were considered against the properties of the Substance. Extracts of the applicability and limitation from the repective OECD guidlines for each study have been highlight below.

OECD 442E (h-CLAT) – The guidelines state, “Test chemicals with a Log Kow greater than 3.5 tend to produce false negative results. Therefore negative results with test chemicals with a Log Kow greater than 3.5 should not be considered.”

OECD 442D (ARE-Nrf2 Luciferase Test Method) – The guidelines state, Test substances with a LogP of up to 5 have been successfully tested whereas extremely hydrophobic substances with a LogP above 7 are outside the known applicability of the test method.”

OECD 442C – The guidelines state, “The current prediction model cannot be used for complex mixture of unknown composition or for substances of unknown or variable composition, complex reaction products or biological materials (i.e. UVCB substances) due to the defined molar ration of test chemical and peptide.”

The Substance is considered to be extremely hydrophobic and has a Log Kow of 7.8 - 8.3 and additionally it is considered to be a UVCB. Data generated from the in vitro approaches are normally considered in the context of integrated approaches and individual studies are to be used as a weight of evidence. Based physical chemical characteristics of the Substance there is high uncertainty regarding the applicability of the current in vitro studies, therefore the predictions are unlikely to be meaningful and/or represent the true hazard of the Substance. In conclusion it was considered appropriate to conduct an in vivo study approach to minimise the uncertainty for this Substance.
Interpretation of results:
study cannot be used for classification
Remarks:
waived
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The skin sensitisation study was conducted on the registered substance according to OECD Testing Guideline 406. Following a challenge exposure with the Substance, dermal scores of 1 or 2 were noted in 19/20 test animals at the 24 -hour observation, and in 20/20 test animals at 48 -hour observation. Based on the result as >15% of the test animals responded at challenge, the test item was classified as sensitising according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures. The Substance will be classified as a skin sensitiser category 1 with the hazard statement H317: May cause an allergic skin reaction. There is insufficient data to classify into sub-categories.