Isooctyl acrylate

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:

other: Study was conducted in compliance with OECD GLP (1997) regulations.

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)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

MTDID 7819CE

IUPAC Name:

MTDID 7819CE

Constituent 2

Reference substance name:

MTDID 7819LS

IUPAC Name:

MTDID 7819LS

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report): MTDID 7819 CE, MTDID 7819LS
- Substance type: Mono-constituent
- Physical state: Liquid
- Analytical purity: 7819CE: 99.61%, 7819LS: 98.79%
- Purity test date: MTDID 7819CE and MTDID 7819LS: 24 Sept, 2015
- Lot/batch No.: MTDID 7819CE:
- Expiration date of the lot/batch: MTDID 7819CE and MTDID 7819LS: 30 November 2016
- Storage condition of test material: At room temperature.

In vivo test system

Test animals

Species:

mouse

Strain:

other:

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janier, Le Genest-Sint-Isle, France
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: 18.7-23.4 grams
- Housing: Animals were group housed in labeled Makrolon cages (MIII type; height 18 cm) containing sterilized sawdust as bedding
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 November 2015 To: 07 December 2015

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0 (control), 25, 50, or 100% w/w test article

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: Soluble in vehicle
- Irritation: At 100% test article, less than 25% increase in ear thickness was observed

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay (LLNA)
- Criteria used to consider a positive response: If the results indicate a Stimulation Index (SI) or greater than or equal to 3, the test article may be regarded as a skin sensitizer.

TREATMENT PREPARATION AND ADMINISTRATION: The dorsal surface of both ears of each animal was topically treated (25 uL/ear) with the appropriate test article concentration (0, 25, 50, or 100%), at the same time on Days 1, 2, and 3.

Positive control substance(s):

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

Statistics:

The EC3 value (the estimated test article concentration that will yield a SI=3) was determined if possible, using linear interpolation.

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: MTDID 7819CE: 25%: 2.8, 50%: 5.0, 100%: 6.0 MTDID 7819LS: 25%: 3.6, 50%: 3.6, 100%: 9.6 Positive Control animals: 4.7

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: MTDID 7819CE: 25%: 2382, 50%: 4320, 100%: 5116 MTDID 7819LS: 25%: 3061, 50%: 3104, 100%: 8253 Vehicle Control animals: 857 Positive Control animals: 4042

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of the study, the test article shoud be considered to be a skin sensitizer, and the weight of evidence indicates that classification as GHS Category 1B is appropriate. 

Executive summary:

The skin sensitization potential of two samples of CASRN 29590-42-9 (MTDID 7819CE and MTDID 7819LS) was evaluated in a local lymph node assay per OECD 429 and OECD GLP (1997). Based on the results of a pre-screen test, test article concentrations of 25, 50, and 100% were tested in the main test (vehicle: acetone:olive oil 4:1), along with a concurrent positive control (25% alpha-hexylcinnamaldehyde in acetone:olive oil). The dorsal surface of both ears of female mice (5/group) were topically treated (25 uL/ear) with the appropriate test article concentration (0, 25, 50, or 100%), at the same time on Days 1, 2, and 3. Three days after the final exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintigrations per minute (DPM) and a stimulation index (SI) was subsequently calculated for each group. The stimulation indices of MTDID 7819CE at the three concentrations were 2.8, 5.0, and 6.0, and the EC3 was determined to be 27.3%. The stimulation indices of MTDID 7819LS at the three concentrations were 3.6, 3.6, and 9.6; an EC3 could not be determined, because all stimulation indices were >3. The stimulation index of the concurrent positive control was 4.7, which is very similar to the stimulation indices of the positive controls for the other two portions of this study (4.6 and 6.5), in which other acrylate monomers were tested. Based on the results of the study, the test article should be considered to be a skin sensitizer, and the weight of evidence indicates that classification as GHS Category 1B is appropriate.