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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 April 2015 - 20 April 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The study was performed as a data requirement for a registration in China.

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 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
2010
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
July 2010
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
2003
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
d.d. 03 November 2015
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
420-990-1
EC Name:
-
Cas Number:
146421-65-0
Molecular formula:
C20H36N2O6
IUPAC Name:
4-(ethenyloxy)butyl N-[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamate
Constituent 2
Chemical structure
Reference substance name:
4-(ethenyloxy)butyl N-{6-[({[6-({[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamoyl}oxy)hexyl]oxy}carbonyl)amino]hexyl}carbamate
Cas Number:
1516571-16-6
Molecular formula:
C34H62N4O10
IUPAC Name:
4-(ethenyloxy)butyl N-{6-[({[6-({[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamoyl}oxy)hexyl]oxy}carbonyl)amino]hexyl}carbamate
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): Uralac P 1920C
- Appearance: Colourless to light yellow flakes

In vivo test system

Test animals

Species:
mouse
Strain:
CBA:J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Nulliparous and non-pregnant: Yes
- Age at study initiation: approx 9 - 11 weeks old
- Weight at study initiation: 19 - 24 g
- Housing: Animals were group housed in labeled Makrolon cages (MIII type; height 18 cm) containing sterilised sawdust as bedding material. Paper and shelters were supplied as cage-enrichment. The animals were group housed in Makrolon MII type cages with a sheet of paper instead of sawdust and cage enrichment on day 6 of the study.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

Diet, water, bedding and cage enrichment evaluations for contaminants and/or nutrients were performed according to facility standard procedures. There were no findings that could interfere with the study.


ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): >= 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
methyl ethyl ketone
Concentration:
5%, 10%, 30% (w/w)
No. of animals per dose:
5
Details on study design:
RANGEFINDING TEST
Two test substance concentrations were tested on two animals; a 10% and 30% concentration. The highest concentration was the highest concentration that could be prepared homogeneously. The test system, procedures and techniques were identical as those used in the main study except that the animals were approximately 10-11 weeks (at initiation of treatment) and that the assessment of lymph node proliferation and necropsy were not performed.

MAIN STUDY
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: If the results indicate an SI ≥ 3, the test substance may be regarded as a skin sensitizer.

ANIMAL ASSIGNMENT
Three groups of five animals were treated with one test substance concentration per group. One group of five animals was treated with vehicle.

Induction - Days 1, 2 and 3; Excision of nodes - Day 6; Tissue processing for radioacitivity - Day 6; Radioactivity measurements - Day 7: Performed according to test guidelines.

Observations:
Mortality/Viability: Twice daily.
Body weights: On day 1 (pre-dose) and day 6 (prior to necropsy).
Clinical signs: Once daily on days 1-6 (on days 1-3 within 1 hour after dosing).
Irritation: Once daily on Days 1-6 (on Days 1 - 3 immediately after dosing) according to a numerical scoring system. Furthermore, a description of all other effects was recorded.

TREATMENT PREPARATION AND ADMINISTRATION:
The test substance preparations (w/w) were prepared within 4 hours prior to each dosing. No adjustment was made for specific gravity of the vehicle. The dorsal surface of both ears was topically treated (25 μL/ear) with the test substance, at approximately the same time on each day. The concentrations were stirred with a magnetic stirrer immediately prior to dosing.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
The six-month reliability check with Alpha-hexylcinnamicaldehyde indicate that the Local Lymph Node Assay as performed at WIL research was an appropriate model for testing for contact hypersensitivity.

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
1.6
Test group / Remarks:
5%
Key result
Parameter:
SI
Value:
2.2
Test group / Remarks:
10%
Key result
Parameter:
SI
Value:
1.4
Test group / Remarks:
30%

Any other information on results incl. tables

Results Pre-screen test:

At 10% and 30% test item concentration, no signs of irritation and systemic toxicity were noted.

White test substance remnants were present on the dorsal surface of the ears of both animals at 10% (Days 2 and 3) and of both animals at 30% (entire observation period)

Other results - main study:

Desintegrations per minute (DPM): Mean DPM/animal values for the experimental groups treated with test item concentrations 0, 5, 10, and 30% were 525, 816, 1156 and 738 DPM, respectively.

Skin reactions: No irritation of the ears was observed in any of the animals examined. White test substance remnants were present on the dorsal surface of the ears of all animals treated at 5% (Days 1-3), 10% (Days 1-4) and 30% (Days 1-5 and/or 6)

Bodyweight: Body weights and body weight gain of experimental animals remained in the same range as controls

Systemic toxicity: No mortality occurred and no clinical signs of systemic toxicity were observed

Macroscopy of the auricular lymph nodes: All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on an LLNA performed according to OECD guideline 429 and under GLP principles, URALAC P 1920C is concluded not to be a skin sensitizer.
Executive summary:

An LLNA was performed with URALAC P 1920C according to OECD guideline 429 and under GLP principles. Three experimental groups of five female CBA/J mice were treated with test substance concentrations of 5, 10 or 30% w/w. No irritation of the ears was observed in any of the animals examined. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals. Mean DPM/animal values for the experimental groups treated with test substance concentrations 5, 10 and 30% were 816, 1156 and 738 DPM, respectively. The mean DPM/animal value for the vehicle control group was 525 DPM. The SI values calculated for the substance concentrations 5, 10 and 30% were 1.6, 2.2 and 1.4, respectively.

Since there was no indication that the test substance elicits a SI ≥ 3 when tested up to 30%, URALAC P 1920C was not considered to be a skin sensitizer. It was established that the EC3 value (the estimated test substance concentration that will give a SI =3) (if any) exceeds 30%.

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