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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Start Date: January 16, 2012 End Date: February 24, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed accrding to recognised method, and conducted in accordance with the Declaration of Helsinki, the ICH. Guideline E6 for Good Clinical Practice, and the testing company's Standard Operating Procedures, and approved protocol.
Qualifier:
no guideline available
Principles of method if other than guideline:
This trial has been conducted in accordance with the Declaration of Helsinki, the ICH. Guideline E6 for Good Clinical Practice, the requirements of 21 CFR Parts 50 and 56, other applicable laws and regulations, the testing company's Standard Operating Procedures, and the approved protocol.
GLP compliance:
no
Remarks:
Not GLP study. Trial conducted according to the Declaration of Helsinki, the ICH. Guideline E6 for Good Clinical Practice, 21 CFR Parts 50 and 56, other applicable laws and regulations, the testing company's SOPs, and the approved protocol.
Type of study:
other: Repeat Insult Patch Test
Species:
human
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Participants:
Fifty-six (56) qualified subjects, male and female, ranging in age from 18 to 67 years, were selected for this evaluation. Fifty-one (51) subjects completed this study. The remaining subjects discontinued their participation for various reasons, none of which were related to the application of the test material.

Inclusion Criteria:
a. Male and female subjects, age 16 (with parental or guardian consent) and over.
b. Absence of any visible skin disease which might be confused with a skin reaction from the test material.
c. Prohibition of use of topical or systemic steroids and/or antihistamines for at least seven days prior to study initiation.
d. Completion of a Medical History form and the understanding and signing of an Informed Consent form.
e. Considered reliable and capable of following directions.

Exclusion Criteria:
a. Ill health.
b. Under a doctors care or taking medications) which could influence the outcome of the study.
c. Females who are pregnant or nursing.
d. A history of adverse reactions to cosmetics or other personal care products.

Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (ca. 2ml)
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (ca. 2ml)
No. of animals per dose:
56 (51 completed study)
Details on study design:
Methodology:
The upper back between the scapulae served as the treatment area. Approximately 2 ml of the test material, or an amount sufficient to cover the contact surface, was applied to the 1x1 absorbent pad portion of a clear adhesive dressing. This was then applied to the appropriate treatment site to form a semi-occlusive patch.
Induction Phase:
Patches were applied three (3) times per week (e.g., Monday, Wednesday, and Friday) for a total of nine (9) applications. The site was marked to ensure the continuity of patch application. Following supervised removal and scoring of the first Induction patch, participants were instructed to remove all subsequent Induction patches at home, twenty-four hours after application. The evaluation of this site was made again just prior to reapplication. If a participant was unable to report for an assigned test day, one (1) makeup day was permitted. This day was added to the induction period.
With the exception of the first supervised induction Patch reading, if any test site exhibited a moderate (2-level) reaction during the Induction Phase, application was moved to an adjacent area. Applications were discontinued for the remainder of this test phase, if a moderate (2-level) reaction was observed on this new test site. Applications would also be discontinued if marked (3-level) or severe (4-level) reactivity was noted.
Rest periods consisted of twenty-four hours following each Tuesday and Thursday removal, and forty-eight hours following each Saturday removal.
Challenge Phase:
Approximately two (2) weeks after the final Induction patch application, a Challenge patch was applied to a virgin test site adjacent to the original Induction patch site, following the same procedure described for Induction, The patch was removed and the site scored at the clinic twenty-four and seventy two hours post-application.

Evaluation Criteria (Erythema and additional Dermal Sequelae):
0 = No visible skin reaction
0.5 = Barely perceptible
1 = Mild
2 = Moderate
3 = Marked
4 = Severe

E = Edema
D = Dryness
S Staining
P = Papules
V Vesicles
B = Bullae
U = Ulceration
Sp = Spreading

Erythema was scored numerically according to this key. If present, additional Dermal Sequelae were indicated by the appropriate letter code and a numerical value for severity.
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
ca 2ml (100%)
No. with + reactions:
0
Total no. in group:
51
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: ca 2ml (100%). No with. + reactions: 0.0. Total no. in groups: 51.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
ca 2ml (100%)
No. with + reactions:
0
Total no. in group:
51
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: ca 2ml (100%). No with. + reactions: 0.0. Total no. in groups: 51.0.

The results of each participant are appended, see table below.

Observations remained negative throughout the test interval.

Under the conditions of this study, test material, Coco-Oleic Estolide Ester DI, did not indicate a potentioal for dermal irritation or allergic contact sensitisation.

Subject Number Initials Age Sex 24*hr Induction Phase Virgin Challenge Site
1 2 3 4 5 6 7 8 9 24*hr 72 hr
1 TLH 49 M 0 0 0 0 0 0 0 0 0 0 0 0
2 J-G 48 M 0 0 0 0 0 0 0 0 0 0 0 0
3 MJM 27 M 0 0 0 0 0 0 0 0 0 0 0 0
4 DML 48 F 0 0 0 0 0 0 0 0 0 0 0 0
5 DAJ 55 F 0 0 0 0 0 0 0 0 0 0 0 0
6 J-G 61 F 0 0 0 0 0 0 0 0 0 0 0 0
7 DPI 46 F 0 0 0 0 0 0 0 0 0 0 0 0
8 IMZ 61 F 0 0 0 0 0 0 0 0 0 0 0 0
9 A-V 33 F 0 0 0 0 0 0 0 0 0 0 0 0
10 MMA 49 F 0 0 0 0 0 0 0 0 0 0 0 0
11 NIB 42 F 0 0 0 0 0 0 0 0 0 0 0 0
12 A-G 51 M 0 0 0 0 0 0 0 0 0 0 0 0
13 MPB 45 F 0 0 0 0 0 0 0 0 0 0 0 0
14 M-J 56 F 0 0 0 0 0 0 0 0 0 0 0 0
15 KLR 56 F 0 0 0 0 0 0 0 0 0 0 0 0
16 LAV 64 F 0 0 0 0 0 0 0 0 0 0 0 0
17 L-M 54 F 0 0 0 0 0 0 0 0 0 0 0 0
18 C-V 34 F 0 0 0 0 0 0 0 0 0 0 0 0
19 CVC 37 F 0 0 0 0 0 0 0 0 0 0 0 0
20 MGC 38 F 0 0 0 DID NOT COMPLETE
21 C-V 65 F 0 0 0 0 0 0 0 0 0 0 0 0
22 LMF 67 F 0 0 0 0 0 0 0 0 0 0 0 0
23 AAK 20 F 0 0 0 0 0 0 0 0 0 0 0 0
24 Y-F 47 F 0 0 0 0 0 0 0 0 0 0 0 0
25 CAB 18 M 0 0 0 0 0 0 0 0 0 0 0 0
26 P-S 34 F 0 0 0 0 0 0 0 0 0 0 0 0
27 CEG 57 F 0 0 0 0 0 0 0 0 0 0 0 0
28 R-Z 46 F 0 0 0 0 0 0 0 0 0 0 0 0
29 JAR 66 M 0 0 0 0 0 0 0 0 0 0 0 0
30 J-R 32 M 0 0 0 0 0 0 0 0 0 0 0 0
31 AMC 39 F 0 0 0 0 0 0 0 0 0 0 0 0
32 DMC 47 F 0 0 0 0 0 0 0 0 0 0 0 0
33 LBB 59 F 0 0 0 0 0 0 0 0 0 0 0 0
34 CLH 51 F 0 0 0 0 0 0 0 0 0 0 0 0
35 RLD 33 F 0 0 0 0 0 0 0 0 0 0 0 0
36 SAM 33 F 0 0 0 0 0 0 0 0 0 0 0 0
37 MSC 23 M 0 0 0 0 0 0 0 0 0 0 0 0
38 RMM 39 F 0 0 0 0 0 0 0 0 0 0 0 0
39 A-T 33 F 0 0 0 0 0 0 0 0 0 0 0 0
40 N-C 55 F 0 0 0 0 0 0 0 0 0 0 0 0
41 SBC 53 F 0 0 0 0 0 0 0 0 0 0 0 0
42 TAW 43 F 0 DID NOT COMPLETE
43 M-V 57 F 0 0 0 0 0 0 0 0 0 0 0 0
44 ABJ 22 F 0 0 0 0 0 0 0 0 0 0 0 0
45 SEW 23 M 0 0 0 0 0 0 0 0 0 0 0 0
46 MMM 59 F 0 0 0 0 0 0 0 0 0 0 0 0
47 TAW 46 F 0 0 0 0 0 0 0 0 0 0 0 0
48 SBW 26 M 0 0 0 0 0 0 0 0 0 0 0 0
49 RLB 36 M 0 0 0 0 0 0 0 0 0 0 0 0
50 SLA 37 F 0 0 0 0 0 0 0 0 0 0 0 0
51 TSC 23 F 0 0 0 0 0 0 0 0 0 0 0 0
52 R-P 23 M 0 0 0 0 0 0 0 0 0 0 0 0
53 ECM 19 M DID NOT COMPLETE
54 ASH 19 M DID NOT COMPLETE
55 SEE 20 F 0 0 0 0 0 0 0 0 0 0 0 0
56 KRS 20 F 0 0 DID NOT COMPLETE
24* = Supervised removal of 1st induction and challenge patch
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Observations remained negative throughout the test interval.
Under the conditions of this study, test material, Coco-Oleic Estolide Ester DI, did not indicate a potential for dermal irritation or allergic contact sensitization.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Migrated from Short description of key information:
In a study of 56 voulenteers in which 51 completed the trial, no adverse effects were seen relating to the test item.

Justification for selection of skin sensitisation endpoint:
HRIPT selected due to the good quality of the data, but also with regard to the questionable efficacy in assessment via the LLNA study, as highlighted by the available published knowledge on similar such substances.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Migrated from Short description of key information:
No study available

Justification for classification or non-classification

In the weight of evidence submitted, two studies specifically have been reported, An LLNA performed in 2013, and a HRIPT study, carried out in 2012. The classification has been determined based on the results of the HRIPT, with due recognition of the results highlighted in the LLNA study, which have been disregarded due to the reasons elaborated below regarding calculation of the Stimulation Index in the study.

In accordance with the findings of the Human Repeat Insult Patch test, the substance is considered not classified for skin sensitisation.

 

HRIPT - CPTC (2012)

This study was carried out with the aid of 56 volunteers, 51 of whom went on to complete the trail, 5 did not continue their participation for reasons unrelated to the application of the test substance.

During the course of the study, no adverse effects were observed or reported, allowing for the conclusion that the substance was not a skin sensitiser.

 

LLNA - MB Research Laboratories (2013)

In the in vitro LLNA study provided a stimulation index of 2.8 was reported, highlighting a potential for skin sensitisation. However, whereas the study was reportedly conducted in accordance with OECD 442B, the results have not been calculated in accordance with the guideline.

The Stimulation Index (SI) for the 100% test item-treated group was calculated to be 2.8 (hence the ‘positive’ result). This was derived by dividing the mean optical density of the 100% test-item treated group by the mean optical density of the naïve (sham treated) group. However, according to OECD test guideline 442B, paragraph 30, “The SI is derived by dividing the mean BrdU labelling index/mouse within each test substance group, by the mean BrdU labelling index for the solvent/VC group.” Note, the solvent/vehicle control group, not the naïve (sham treated) group. The SI for the 100% test item-treated group, if calculated according to OECD 442B is 1.44 (0.243/0.169) which will be below the 1.6 threshold and therefore highlights a negative result.

See the table below for mean values recalculated using the method prescribed in OECD 442B, and the values reported in the table of Stimulation Index Values from the study summary.

Treatment Mean OD SI 
AOO
(Vehicle Control)		 0.169
25% HCA
(Positive Control)		 0.314 1.86
25% (v/v)
CAS# 1365345-64-7
(SE7B Batch 2137-0)		 0.159 0.94
50% (v/v)
CAS# 1365345-64-7
(SE7B Batch 2137-0)		 0.167 0.99
100% (v/v)
CAS# 1365345-64-7
(SE7B Batch 2137-0)		 0.243 1.44

Kreiling et al (2008) and Ball, N et al (2011)

These papers has been included to highlight the uncertainty of LLNA studies performed on several surfactants in one and several unsaturated compounds in the other (which share similar properties to the test substance) albeit in accordance with OECD 429 rather than 442B.

The report shows a significant potential for LLNA studies in such materials to provide positive results which are at odds with several other recognised test methods, assays and structural alerts. These have been included to add weight to the argument that the result of the HRIPT should be given merit over the LLNA performed according to 442B.