5,9-dimethyl-4,8-decadienal

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 September, 2015 - 09 December, 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

skin sensitisation, other

Remarks:

Read-across

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The information is derived from read across

Justification for type of information:

Executive summary: The skin sensitization of Geraldehyde is assessed by using read across from Profarnesal (CAS 54082-68-7) resulting in presence of skin sensitization for Geraldehyde. Full details are provided in the study record. Structural similarity and differences: The structures of the source and target chemicals are very similar, which can already be seen from the chemical names: 2,6,10-trimethylundeca-5,9-dienal (Profarnesal) and 5,9-dimethyldeca-4,8-dienal (Geraldehyde); both have a C10 or C11 backbone with two isolated double bonds (terpenoid fragments) and two or three methyl groups along this alkyl chain. Both substances are aldehydes and these functional groups are considered to be mainly responsible for the skin sensitizing potential. Toxico-kinetic relevant for skin sensitization: The dermal bioavailability can be assessed using the molecular weight, appearance and physico-chemical properties of both substances. Both substances are liquids. The 2Cs longer alkyl chain of Profarnesal results in a somewhat higher log Kow and lower water solubility compared to Geraldehyde, but this will not significantly change the dermal bioavailability also because both substances are liquids. Toxico-dynamics: Both substances are alkyl aldehydes and these aldehydes are predicted to have similar reactivity. The terpenoid functionality present in both substances is prone to auto oxidation and thus hydrogen peroxide formation. The presence of these groups results in similar reactivity. Remaining uncertainties: There is no remaining uncertainty as presented in the reasoning above.

Reason / purpose for cross-reference:

read-across source

Parameter:

SI

Remarks on result:

other: The SI values calculated for the substance concentrations 25, 50, and 100% were 1.9, 3.5 and 3.4, respectively.

Key result

Parameter:

EC3

Remarks:

%

Value:

42.3

Parameter:

other: NOEC %

Value:

25

Interpretation of results:

other: Skin sensitising (category 1B)

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

Based on the data available it can be concluded that the substance is a skin sensitiser.

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:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

1

Reference substance name:

Reference substance 001

Cas Number:

54082-68-7

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Jcr

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley; Indianapolis, IN
- Age at study initiation: 8 weeks
- Weight at study initiation: 18.8 - 24.0 g (on initial dose day)
- Housing: One to five animals in polycarbonate box with bedding.
- Diet: Free access to PMI Feeds Inc. TM Formulab #5008
- Water: Free access to municipal water
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS (target ranges)
- Temperature (°C): 20 - 23
- Humidity (%): 30 - 94
- Air changes (per hr): 10+
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

Undiluted test item or the test item at concentrations of 25% or 50% v/v in vehicle.

No. of animals per dose:

5

Details on study design:

A range finding test was not conducted for this study.

TREATMENT PROCEDURES:
TOPICAL APPLICATION:
On Days 1, 2 and 3, each test animal in its group received an open application of 25 μL of appropriate dilution (25 or 50%) of test item in vehicle, or l 00% test item, to the dorsum of both ears. The vehicle control group (5 females) was treated the same way as test animals, but with vehicle alone instead of test item. The positive control group (5 females) was treated with 100% alpha-hexylcinnamaldehyde. All test and control animals were given a two-day rest period on Days 4 and 5.

ADMINISTRATION OF 3H-METHYL THYMIDINE:
On Day 6 of the study, all test and control animals were injected in the tail vein with 250 μL of 0.01 M phosphate-buffered saline (PBS; Sigma, Lot SLBJS 11 OV, Exp Jun 2024), pH 7.4 at 25°C per manufacturer, containing 20 μCi of [methyl-3H] Thymidine (PerkinElmer, Lot 201511, Exp 6 Nov 16). Five hours after injection, animals were sacrificed with an overdose of C02, the draining auricular lymph nodes excised and pairs from each individual animal processed.

DETERMINATION OF INCORPORATED 3HTdR:
A single cell suspension was prepared by gentle mechanical disintegration through 200 mesh stainless steel gauze. Cells were washed twice with an excess of PBS and precipitated with 5% trichloroacetic acid (TCA; Ricca, Lot 250882311511892, Exp Jul/Nov 20 16) at 4°C for 18 hours. The pellets were resuspended in 1 mL of TCA and transferred to 10 mL of scintillation fluid. Incorporation of tritiated thymidine was measured by liquid scintillation counting as disintegrations per minute (DPM) from paired lymph nodes of each animal, and mean DPM/animal was calculated for each group. Background DPM values, determined by blanks, are automatically subtracted by the scintillation counter.

OBSERVATIONS:
Individual body weights were recorded on Day 1 prior to dosing, and Day 6, prior to injection. All test and control animals were observed daily for clinical signs of toxicity and any excessive irritation at the test site.

Positive control substance(s):

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

Statistics:

A one-way parametric analysis of variance (ANOVA) with Dunnett's Multiple Comparisons Test, using GraphPad InStat version 3.06 for Windows 95, GraphPad Software, San Diego California USA, was performed on DPM counts.

Results and discussion

Positive control results:

The positive control item, hexyl cinnamic aldehyde, gave a Stimulation Index of 5.2 when tested at a concentration of 100% v/v in acetone/olive oil 4:1.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: The SI values calculated for the substance concentrations 25, 50, and 100% were 1.9, 3.5 and 3.4, respectively.

Results 2

Key result

Parameter:

EC3

Remarks:

%

Value:

42.3

Results 3

Parameter:

other: NOEC %

Value:

25

Any other information on results incl. tables

Results:

Animal group	Test item concentration	Average DPM count per mouse	Number of mice in group	Test/vehicle control ratio (SI)
Vehicle control	NA	2405	5	NA
Test group I	25%	4649	5	1.9
Test group II	50%	8368	5	3.5
Test group III	100%	8274	5	3.4
Positive control	NA	12508	4	5.2

VIABILITY / MORTALITY:

One Positive Control animal was found dead following Day 6 injection.

CLINICAL SIGNS:

All animals appeared normal for the duration of the study.

BODY WEIGHTS:

Four of both Test Group II and III animals lost or failed to gain weight during the study; some animals in both control groups also lost weight.

Applicant's summary and conclusion

Interpretation of results:

other: Skin sensitising (category 1B)

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

The SI values calculated for the substance concentrations 25, 50 and 100% were 1.9, 3.5 and 3.4, respectively. These results show that the test substance could elicit a SI ≥ 3. An EC3 has been derived resulted in an EC3 of 42.3%. A NOEC of 25% is derived. The test substance was considered to be a sensitiser under the conditions of the test.

Executive summary:

The skin sensitisation potential of the substance has been tested according to OECD TG 429 and GLP principles. At 25, 50 and 100% the substance showed SI values of 1.9, 3.5 and 3.4, respectively. Reliable negative and positive controls were included. All animals appeared normal for the duration of the study.

These results show that the test substance could elicit a SI ≥ 3. An EC3 has been derived resulted in an EC3 of 42.3%. A NOEC of 25% is derived.

Based on the results, the substance is considered to be a skin sensitiser.