Allyltrimethylsilane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 April - Jul 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

22 July 2010

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

06 July 2012

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Hessisches Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Allyltrimethylsilane

EC Number:

212-104-5

EC Name:

Allyltrimethylsilane

Cas Number:

762-72-1

Molecular formula:

C6H14Si

IUPAC Name:

allyltrimethylsilane

Test material form:

liquid

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/CaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Postbus 6174, 5960 AD Horst / The Netherlands
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 18.5 ± 1.6
- Housing: group housed in Makrolon Type II (pre-test) / III (main study), with wire mesh top
- Diet: 2018C Teklad Global 18% protein rodent diet (certified), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 45-65
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): artificial light 6.00 a.m. - 6.00 p.m.

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

25, 50, and 100% in acetone/olive oil (4+1, v/v)

No. of animals per dose:

4 females/group

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: A solubility experiment was performed according to the recommendations given by OECD 429. The highest test item concentration, which could be technically used was 100% (undiluted test item).
- Irritation: Local irritation were documented and a score was used to grade a possible erythema of the ear skin.
- Systemic toxicity: Clinical signs were recorded at least once daily. The body weights were recorded on day 1 (prior to dosing) and prior to treatment with 3HTdR.
- Ear thickness measurements: In the pre-test, the ear thickness was determined prior to the first application of the test item (day 1), on day 3, and on day 6 prior to sacrifice using a micrometer.
- Erythema scores: Measured according to Draize.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the Stimulation Index. Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION: Each test group of mice was treated by (epidermal) topical application to the dorsal surface of each ear with test item concentrations of 25, 50, and 100% in acetone/olive oil (4+1, v/v). The test material was applied to each ear once daily for three consecutive days. A further group of mice (control animals) was treated with an equivalent volume of the relevant vehicle alone (control animals). Five days after the first topical application, phosphate-buffered saline containing 3H-methyl thymidine was injected into each test and control mouse via the tail vein. Approximately five hours after treatment with 3HTdR all mice were euthanized after harvesting of the lymph nodes, followed by cervical dislocation. Harvested lymph nodes were dailed and pooled for each experimental group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a beta-scintillation counter.

Positive control substance(s):

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

Statistics:

None reported

Results and discussion

Positive control results:

The positive control showed a positive response, with SI of 1.48, 2.26, and 8.10 for 5, 10, and 25% of alpha-hexylcinnamaldehyde in acetone:olive oil (4:1 v/v), respectively.

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1.16

Test group / Remarks:

25%

Results 2

Key result

Parameter:

SI

Value:

1.04

Test group / Remarks:

50%

Results 3

Key result

Parameter:

SI

Value:

1.21

Test group / Remarks:

100%

Results 4

Key result

Parameter:

EC3

Remarks on result:

not determinable

Remarks:

The EC3 value could not be calculated, since none of the tested concentrations induced a S.I. greater than the threshold value of 3

Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION : In this study Stimulation Indices (S.I.) of 1.36, 1.04, and 1.21 were determined with the test item at concentrations of 25 and 50% in acetone/olive oil (4+1, v/v), and 100% (undiluted test item), respectively.

EC3 CALCULATION : The EC3 value could not be calculated, since none of the tested concentrations induced a S.I. greater than the threshold value of 3.

CLINICAL OBSERVATIONS: All treated animals survived the scheduled study period and no signs of systemic toxicity were observed. On day 3, all animals treated with the test item showed a very slight erythema of the ear skin (Score 1). The animals treated with the undiluted test item continued to show an erythema of the ear skin on test days 4 and 5. Additionally, the animals treated with 100% test item showed scaly ears.

BODY WEIGHTS: The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.

Conclusions:

In an OECD and GLP compliant LLNA study, the test item allyltrimethylsilane was not a skin sensitiser.