2,3,3,4,4-pentafluoro-5-methoxy-2,5-bis[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]tetrahydrofuran

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016

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

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

2010

Deviations:

yes

Remarks:

Deviations from the maximum level of daily mean relative humidity occurred. Laboratory historical data do not indicate an effect on the study.

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

2,3,3,4,4-pentafluoro-2,5-bis(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-5-methoxyoxolane

EC Number:

812-244-2

Cas Number:

957209-18-6

Molecular formula:

C11H3F19O2

IUPAC Name:

2,3,3,4,4-pentafluoro-2,5-bis(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-5-methoxyoxolane

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot # 20003, unit 0022
- Expiration date of the lot/batch: 30 March, 2018
- Purity test date: 30 March, 2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Solubility and stability of the test substance in the solvent/vehicle: The vehicle was selected on the bases of maximizing the solubility of the test article.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was dissolved in methyl ethyl ketone.

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
- Females (if applicable) nulliparous and non-pregnant: Yes
- Microbiological status of animals, when known: No data
- Age at study initiation: Approximately 10 weeks
- Weight at study initiation: Mean: 22.43 grams
- Housing: Animals were group housed in labelled Makrolon cages (MIII type; height 18 cm) containing sterilised sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany). Paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom) and shelters (disposable paper corner home, MCORN 404, Datesand Ltd, USA) were supplied as cage-enrichment.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z SSNIFF Spezialdiaten GmbH, Soest, Germany), ad libitum.
- Water (e.g. ad libitum): Tap water, ad libitum.
- Acclimation period: At least 5 days before the start of treatment.
- Indication of any skin lesions: None

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 12 July, 2016 To: 03 August, 2016

Study design: in vivo (LLNA)

Vehicle:

methyl ethyl ketone

Concentration:

0 (Methyl ethyl ketone), 25, 50, and 100 % w/w

No. of animals per dose:

5

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: Soluble
- Irritation: No erythema was observed. Scaliness was noted in the animals treated at 50 and 100% on Days 2 and 3 but was not considered to have a toxicologically significant effect on the activity of the nodes.
- Systemic toxicity: Not observed.
- Ear thickness measurements: Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values.
- Erythema scores: 0

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local lymph node assay
- Criteria used to consider a positive response: If the results indicated a Stimulation Index of greater than or equal to 3, the test article is regarded as a skin sensitizer.

TREATMENT PREPARATION AND ADMINISTRATION: Induction: Days 1, 2, and 3: The dorsal surface of both ears were topically treated (25 uL/ear) with the test article, at approximately the same time each day. The solutions were stirred with a magnetic stirrer immediately prior to dosing. The control animals were treated in the same way as the experimental animals, except the vehicle was administered instead of the test article.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

A positive control reliability check was performed within 6 months of this study and indicated that the test system was appropriate.

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

ca. 1.3

Test group / Remarks:

100% Test article

Results 2

Parameter:

SI

Value:

ca. 1

Test group / Remarks:

50% Test article

Results 3

Parameter:

SI

Value:

ca. 1.2

Test group / Remarks:

25% Test article

Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION: Mean DPM values were 438, 349 and 474 DPM for 25, 50, and 100% test article, respectively.

EC3 CALCULATION: An EC3 was not calculated as an SI of 3 was not reached at 100% test article.

CLINICAL OBSERVATIONS: No erythema was observed in any animals. The scaliness shown by animals throughout all dosing groups between Days 1 and was considered not to have a toxicologically significant effect on the activity of the nodes. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals.

BODY WEIGHTS: Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, the test article is not considered a skin sensitizer as it elicited an SI value of 1.3 when tested at 100%.

Executive summary:

The dermal sensitization potential of the test article was evaluated in the local lymph node assay (LLNA) with female CBA/J mice. The study was performed in compliance with OECD GLP (1997). The test method was performed according to OECD 429 (2010). The test article was prepared in methyl ethyl ketone at 0 (control), 25, 50 and 100% (w/w). Female mice (5/treatment) received the negative control (Methyl ethyl keton), 25, 50, or 100% concentrations of the test substance. The corresponding treatment (25 uL/ear) was applied to the dorsal surface of both ears for three consecutive days. Three days after the last exposure (Day 6), all animals were injected with 0.25 mL sterile phosphate buffered saline containing 3 H-methyl thymidine and subsequently euthanized. The nodes were pooled for each animal, and lymphocyte proliferation was determined by measuring disintegrations per minute (DPM). The stimulation index (SI) was calculated for each group. Observations for mortality (once daily), body weights (Day 1 and Day 6), clinical signs (once daily), ear thickness (Days 1-3, and Day 6), and irritation (Days 1-3 and 6) were performed as well. Mean DPM/animal values were 438, 349 and 474 DPM for 25, 50, and 100% test article, respectively. The mean DPM/animal value for the vehicle control group was 366. The SI values calculated for the test item concentrations of 25, 50, and 100% were 1.2, 1.0 and 1.3, respectively. Based on the results of the study, the test article is not considered a skin sensitizer as it elicitied an SI value of 1.3 when tested at 100%.