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Description of key information

Data for this endpoint comprises of a weight of evidence approach using in vivo data and an silico QSAR predictions. These include results of three Local Lymph Node Assays (LLNA), and LLNA QSAR prediction and two human studies (patch test and repeat insult patch test).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation, other
Remarks:
in silico prediction using TOPS-MODE approach
Type of information:
(Q)SAR
Adequacy of study:
other information
Study period:
2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
no guideline required
Principles of method if other than guideline:
The TOPS-MODE (topological substructural molecular descriptors) involves developing linear QSARs using the spectral moments of a molecular bond matrix. QSARs developed using these moments contain encrypted structural information, which can hence be transformed into quantitative contributions for each bond in the molecule, so-called bond contributions. These bond contributions are used to formulate structural rules describing those features of the molecule that drive a specific mechanism of action as well as identifying potential pharmacophores and/or toxicophores.
GLP compliance:
not specified
Justification for non-LLNA method:
No justification provided.
Specific details on test material used for the study:
Not applicable. Study is a QSAR prediction.
Species:
mouse
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Not applicable. Study is a QSAR prediction.
Key result
Parameter:
other: LLNA prediction made using TOPS-MODE approach.
Value:
5.5
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
positive indication of skin sensitisation
Other effects / acceptance of results:
TOPS-MODE model classified the result as a 'class 1 sensitiser' - signifying strong and moderate sensitisers.

The TOPS-MODE QSAR model derived a LLNA EC3 value of 5.5. The model also classified the result as a 'class 1 sensitiser' - signifying strong and moderate sensitisers.

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
The TOPS-MODE QSAR model derived a LLNA EC3 value of 5.5. The model also classified the result as a 'class 1 sensitiser' - signifying strong and moderate sensitisers. Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).
Executive summary:

The TOPS-MODE QSAR model derived a LLNA EC3 value of 5.5. The model also classified the result as a 'class 1 sensitiser' - signifying strong and moderate sensitisers.  Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2008
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Qualifier:
equivalent or similar to guideline
Guideline:
other: Local Lymph Node Assay; details on guidelines not specified.
Deviations:
not specified
Principles of method if other than guideline:
Local Lymph Node Assay; no further details on the method were reported.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
No details reported.
Species:
mouse
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No details reported.
Vehicle:
not specified
Concentration:
No details reported.
No. of animals per dose:
No details reported.
Details on study design:
No details reported.
Positive control substance(s):
not specified
Statistics:
No details reported.
Key result
Parameter:
EC3
Value:
4.048
Remarks on result:
other: LLNA weighted mean EC3 value ( 1012 μg/cm2); converted to 4.048 % concentration based on the assumption that the application of 25 μl of a 1 % solution results in a dose per unit area of 250 μg/cm2.
Remarks:
Considered 'moderate'
Parameter:
SI
Variability:
No details reported
Test group / Remarks:
No details reported
Remarks on result:
other: No details reported
Cellular proliferation data / Observations:
No details reported.
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
The LLNA EC3 value was reported as a weighted mean of two studies with a value of 1012 μg/cm2. The authors reported this value to be a 'moderate' skin sensitiser. Assuming that the application of 25 μl of a 1 % solution results in a dose per unit area of 250 μg/cm2 the EC3 value is converted to a percentage concentration of 4.048. Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).
Executive summary:

The LLNA EC3 value was reported as a weighted mean of two studies with a value of 1012 μg/cm2. The authors reported this value to be a 'moderate' skin sensitiser. Assuming that the application of 25 μl of a 1 % solution results in a dose per unit area of 250 μg/cm2 the EC3 value is converted to a percentage concentration of 4.048. Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
not specified
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
No details reported.
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: No details reported.
- Age at study initiation: 7-12 weeks
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 0.5, 1, 2.5, 5 or 10 %
No. of animals per dose:
Details not reported
Details on study design:
Treatment was performed daily for 3 consecutive days. Five days after the initiation of exposure, all mice were injected via the tail vein with 250 µl of phosphate-buffered saline containing 20 µCi of trilated thymidine. The mice were killed 5 hours later, and the draining auricular lymph nodes were excised and pooled for each experimental group. The incorporation of tritated thymidine measure by beta scintillation counting was reported in disintegrations per minute.
An SI was calculated for each chemical-treated group as the ratio of the disintegrations per minute in the treated group to the disintegrations per minute of the concurrent vehicle control group.
Positive control substance(s):
not specified
Statistics:
No details reported.
Positive control results:
No details reported.
Parameter:
SI
Value:
1.2
Test group / Remarks:
0.5 % dose group
Parameter:
SI
Value:
1.2
Test group / Remarks:
1 % dose group
Parameter:
SI
Value:
2.3
Test group / Remarks:
2.5 % dose group
Parameter:
SI
Value:
2.6
Test group / Remarks:
5 % dose group
Parameter:
SI
Value:
6.4
Test group / Remarks:
10 % dose group
Key result
Parameter:
EC3
Value:
5.5
Test group / Remarks:
Moderate potency category
Cellular proliferation data / Observations:
When the LLNA dose-response curve included concentations that induced at least one SI greater than 3, and one SI less than 3, EC3 values were calculated by linear extrapolation.
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
The results from the mouse Local Lymph Node Assay (LLNA) report give an EC3 value of 5.5 %. The authors have classified this result as a 'moderate' potency category for skin sensitisation.Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).
Executive summary:

Mouse LLNA data derived from previously conducted studies were compiled from published literature. The results give an EC3 value of 5.5 %. The authors have classified this result as a 'moderate' potency category for skin sensitisation.Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: HRL Protocol #100RIFM
Principles of method if other than guideline:
- Principle of test: Repeated Insult Patch Test
- Short description of test conditions: Human volunteers, returning for evaluation at the laboratory 3 days/week.
- Parameters analysed / observed: Sites were scored using the modified scoring scale of the International Contact Dermatitis Research Group System. No other parameters are reported.
GLP compliance:
not specified
Type of study:
patch test
Justification for non-LLNA method:
No details reported.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Referred to as 'H452-1' in the report. No further details reported.
- Expiration date of the lot/batch: No details reported.
- Purity test date: No details reported.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
No details reported.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
No details reported.
Species:
other: Human volunteers
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
No details reported.
Route:
epicutaneous, occlusive
Vehicle:
other: 1:3 EtOH:DEP
Concentration / amount:
0.02%
Day(s)/duration:
24 hours
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
No details reported
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
No details reported.
Day(s)/duration:
48 hours
Adequacy of challenge:
not specified
No.:
#3
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
No details reported
Day(s)/duration:
72 hours
Adequacy of challenge:
not specified
No.:
#4
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
No details reported.
Day(s)/duration:
96 hours
Adequacy of challenge:
not specified
No. of animals per dose:
50 humans
Details on study design:
Each potential subject completed a subject history form including relevant medical history. Each accepted subject was assigned to a permanent Identification Number. Subjects were not used if he or she exhibited any dermatological or other medical or physical condition that would preclude topical application of the test item. No known pregnant nor nursing women were used. Legally informed consent was secured from each subject.

MAIN STUDY

A. INDUCTION EXPOSURE
A webril/adhesive patch (25 mm Hill Top Chamber System (R)) was used occlusively. Using a precise, repeating syringe, 0.3 ml of the test item was applied to each designated patch. The test sites were wiped with a dry Kimwipe (R) prior to each patching. The left side of the back was usually the test area for the Induction Phase. The subject's skin was marked with gentian violet surgical marker at the left side of each test site.
Each subject was instructed that the patches were to remain in place and kept dry for approximately 24 hours, at which time the subject returned to the laboratory for patch removal by a technician (on non-working days the patch was removed by the subject). A series of 9 induction patchings were completed in a period of approximately 3 weeks. A rest period of approximately 2 weeks followed the last induction patching.

B. CHALLENGE EXPOSURE
At the challenge phase, the original induction test sites were observed and each subject queried as to whether any reaction was experienced during the rest period. The right side of the back was usually the virgin test site for the Challenge Phase. At challenge 1 (C1 visit), approximately 24 hours later, the patches were removed and the sites were scored. The original test sites were also observed. Each subject then reported back to the lab at 48 hours (C2 visit), 72 hours (C3 visit) and 96 hours (C4 visit) post-patching for reaction scoring.

Challenge controls:
No details reported
Positive control substance(s):
yes
Positive control results:
No details reported.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 1
No. with + reactions:
0
Total no. in group:
119
Clinical observations:
No visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 2
No. with + reactions:
0
Total no. in group:
115
Clinical observations:
No visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 3
No. with + reactions:
0
Total no. in group:
114
Clinical observations:
No visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 4
No. with + reactions:
0
Total no. in group:
113
Clinical observations:
No visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 5
No. with + reactions:
0
Total no. in group:
112
Clinical observations:
No visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 6
No. with + reactions:
0
Total no. in group:
111
Clinical observations:
No visible reaction
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 7
No. with + reactions:
0
Total no. in group:
111
Clinical observations:
No visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 8
No. with + reactions:
0
Total no. in group:
109
Clinical observations:
No visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Grade 9
No. with + reactions:
2
Total no. in group:
109
Clinical observations:
2 subjectS was observed to have 'faint, minimal erythema'. 1 subject did not have a 9th reading. All other subjects has no visible reactio
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.02 %
No. with + reactions:
0
Total no. in group:
107
Clinical observations:
No visible reaction
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.02 %
No. with + reactions:
0
Total no. in group:
107
Clinical observations:
1 subject was observed to have 'no reading'. All other subjects had no visible reaction.
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
0.02 %
No. with + reactions:
1
Total no. in group:
106
Clinical observations:
1 subject was observed to have erythema and oedema. All other subjects has no visible reaction.
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
96
Group:
test chemical
Dose level:
0.02 %
No. with + reactions:
4
Total no. in group:
106
Clinical observations:
1 subject was reported to have erythema and oedema. 3 subjects were observed to have 'no reading'. All other subjects had no visible reaction.
Remarks on result:
positive indication of skin sensitisation
Reading:
other:
Group:
negative control
No. with + reactions:
0
Total no. in group:
109
Clinical observations:
No visible reaction
Remarks on result:
no indication of skin sensitisation
Reading:
other: 1st reading and rechallenge
Group:
positive control
No. with + reactions:
0
Total no. in group:
109
Clinical observations:
No visible reaction
Remarks on result:
no indication of skin sensitisation

During the testing phase, two subjects exhibited low level, transient reactions. At the challenge, one subject exhibited erythema and oedeam reaction. No other reactions were exhibited. It is reported that in this Repeated Insult Patch Test the test item did induce an oedematous reaction indicative of sensitisation in one human subject. The controls did not induce dermal sensitisation in human subjects.

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
During the testing phase, two subjects exhibited low level, transient reactions. At the challenge, one subject exhibited erythema and oedeam reaction. No other reactions were exhibited. It is reported that in this Repeated Insult Patch Test the test item did induce an oedematous reaction indicative of sensitisation in one human subject. The controls did not induce dermal sensitisation in human subjects. Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).
Executive summary:

During the testing phase, two subjects exhibited low level, transient reactions. At the challenge, one subject exhibited erythema and oedeam reaction. No other reactions were exhibited. It is reported that in this Repeated Insult Patch Test the test item did induce an oedematous reaction indicative of sensitisation in one human subject. The controls did not induce dermal sensitisation in human subjects. Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2004-07-09 to 2005-01-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
The stability and achieved concentration of the test item in the vehicle was not determined by analysis.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
2003
Deviations:
not specified
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Bedoukian, Lot No: 2004134-0015, CTL bottle number 257432
- Expiration date of the lot/batch: 12 December 2006
- Purity test date: 09 November 2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient temperature in the dark
- Stability under test conditions: Under the responsibility of the Sponsor and therefore the stabilty was not determined; no further details reported.
- Solubility and stability of the test substance in the solvent/vehicle: No details reported.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No details reported.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: All dose preparations were used within 24 hours of preparation
- Preliminary purification step (if any): No details reported.
- Final dilution of a dissolved solid, stock liquid or gel: No details reported.
- Final preparation of a solid: No details reported.
Species:
mouse
Strain:
other: CBA/CA/Ola/Hsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Interfauna UK Limited, Blackthorne, Bicester, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Microbiological status of animals, when known: No details reported.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 17.5-19.9 g
- Housing: 4 mice/cage. Caging was cosnidered to be suitable and environmental enrichment was provided (tents, bases and nestlets).
- Diet (e.g. ad libitum): Special Diet Services Limited, available ad libitium
- Water (e.g. ad libitum): Water provided by an automatic system, available ad libitium
- Acclimation period: At least 5 days
- Indication of any skin lesions: No details reported.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 30-70
- Air changes (per hr): A mininium of 15
- Photoperiod: 12 hours dark/12 hours light
Vehicle:
other: 1:3 ethanol:diethyl phthalate
Concentration:
0.51, 1, 2.5, 5 or 10 % w/v preparation (25 microlitres)
No. of animals per dose:
4
Details on study design:
PRE-SCREEN TESTS:
No details reported.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: Results were expressed as a disintergration per minute (dpm) value per lymph node for each group. The activitiy of each test group is then divided by the activity of the vehicle control group to give a test:control ratio for each concentration. The criterion for a positve response is that one or more concentrations of the test item should elicit a 3-fold or greater increase in isotope incorporation relative to the vehicle control group. The estimated concentration of the test item required to produce a 3-fold increase in the draining lymph node cell proliferative assay was calculated (EC3).

EC3 = [(3-d)/(b-d)] x (a-c) +c

Whereby: a = the concentration giving the SI immediatley above 3; b = the SI of a; c = the concentration giving the SI immediatley below 3; d = the SI of c.

The quantity applied per square centimetre was derived from this value, assuming that the area of the mouse ear is 1cm2 and that 1ul is euivalent to 1mg.

Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
No details reported.
Positive control results:
The postive control reuslts confirmed the validity of the study.
Key result
Parameter:
EC3
Value:
2.5
Remarks on result:
other: positive indication of sensitisation
Parameter:
SI
Variability:
No details reported
Test group / Remarks:
No details reported
Remarks on result:
other: SI details not reported
Parameter:
SI
Variability:
No details reported
Test group / Remarks:
No details reported
Remarks on result:
other: SI details not reported
Cellular proliferation data / Observations:
No details reported.
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The test item diluted in the vehicle 1:3 EtOH: DEP is likely to be a skin sensitiser under the conditions of the test. The EC3 value was calculated to be 2.5 % w/v (equivalent to 650 ug/cm2).
Executive summary:

The test item was tested for sensitisatio potential using the mouse local lymph node assay. The test substance was applied in 1:3 EtOH:DEP and the estimated concentration giving rise to a 3 -fold increase in lymphocyte proliferation was calculated.

Results indicate that the test item is likely to be a skin sensitiser under the conditions of the test. The EC3 value was calculated to be 2.5 % w/v (equivalent to 650 ug/cm2).

Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).

Endpoint:
skin sensitisation, other
Remarks:
Human volunteer study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1973
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Maximization test in human volunteers
- Short description of test conditions: Twenty five subjects were exposed to the test item for five alternate-day 48-hour periods.
- Parameters analysed / observed: No details reported.
GLP compliance:
no
Type of study:
patch test
Justification for non-LLNA method:
No details reported.
Specific details on test material used for the study:
No details reported.
Species:
other: Twenty five healthy adult human volunteers
Strain:
other: Not applicable
Sex:
male
Details on test animals and environmental conditions:
No details reported.
Positive control results:
No details reported.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
Not reported
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No instances of contact-sensitisation were reported.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Not reported
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No instances of contact-sensitisation were reported.
Remarks on result:
no indication of skin sensitisation

There were no instances of contact-sensitisation during the test. The authors reported that it was 'unlikely' that the test item would present a danger of contact sensitisation in normal, intended use.

Interpretation of results:
GHS criteria not met
Conclusions:
There were no instances of contact-sensitisation during the test. The authors reported that it was 'unlikely' that the test item would present a danger of contact sensitisation in normal, intended use. Therefore the test item is not classified under GHS criteria.
Executive summary:

There were no instances of contact-sensitisation during the test. The authors reported that it was 'unlikely' that the test item would present a danger of contact sensitisation in normal, intended use.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Justification for classification or non-classification

The three LLNA assays result in EC3 values (effective concentration of the test item that is required to produce a three fold increase in the stimulation index when compared to vehicle controls) that are ≤ 2 % (2.5%, 4.048 % and 5.5 %). This value is further supported by a QSAR conducted using the TOPS MODE method that predicts an EC3 value of 5.5 %.

Of the available human data, the maximisation test (patch test) did not result in a sensitising effect, however this study is not considered to be reliable (reliability score =4). In contrast, the human repeated insult patch test did report a sensitising effect, albeit only in one human subject.

This provides evidence that the sensitising effect observed in animals is relevant to humans. Therefore, the test item is classified as a Category 1A for skin sensitisation (H317) according to CLP criteria (EC Regulation 1272/2008).