Dodecanal

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

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

Adequacy of study:

key study

Study period:

2001-08-28 to 2001-09-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available for the analogue substance, Undec-10-enal. It is a GLP compliant study conducted in compliance with agreed protocols, with no or minor deviations for the standard test. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (Dodecanal) and source substance (Undec-10-enal) and their similar physico-chemical properties.

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

other: CBA/Jlbm (SPF)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division, Wölferstrasse 4, Füllinsdorf, Switzerland.
- Age at study initiation: 7-12 wks
- Weight at study initiation: 17.7 g to 24.8 g
- Parity: Nulliparous and non-pregnant
- Housing: In groups of 4 in Makrolon type-3 cages with standard softwood bedding.
- Diet: Pelletted standard Kilba 3433, batch No. 73/01.
- Water: Tap water, ad libitum.
- Acclimation period: Yes, under test conditions (time not specified), after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature 22 °C ± 3 °C, occasional deviations did not affect integrity of study.
- Humidity: 30 % - 70 %, occasional deviations did not affect integrity of study.
- Air changes: 10-15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

Vehicle:

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

Concentration:

0 % (control), 5 %, 10 %, 25 %, 50 %, 75 % (v/v)

No. of animals per dose:

4 female

Details on study design:

TEST ITEM PREPRARATION
- The test item was placed into a glass beaker on a tared Mettler balance and the vehicle (acetone:olive oil, 4:1 (v/v) was added. A weight by weight dilution was prepared using a magnetic stirrer as a homogeniser. Homogeneity of the test item in the vehicle was maintained during treatment with the magnetic stirrer.
- The preparation was made shortly before each dosing.
- The test item in the main study was assay at 5 consecutive concentrations chosen by the sponsor.

TOPICAL APPLICATION
- Each test group of mice was treated with topical (epidermal) application to the dorsal surface of each earlobe, with different test item concentrations or vehicle control.
- The application volume, 25 µL was spread over the entire dorsal surface of each earlobe once daily for 3 consecutive days.
- A hairdryer was used to dry the surface of the ear as quickly as possible to avoid loss of applied test item.

ADMINISTRATION OF ³H-METHYL THYMIDINE
- ³H-methyl thymidine (³HTdR) was purchased from Amersham International (product code TRA 310, specific activity 2 Ci/mmol, concentration 1 mCi/mL)
- 5 days after the 1st topical application, all mice were administered with 250 µL of 83.32 µCi/mL ³HTdR (equivalent to 20.83 µCi ³HTdR) by intravenous injection via a tail vein.

DETERMINATION OF INCORPORATED ³HTdR
- Approx. 5 hrs after treatment with ³HTdR all mice were euthanised by intraperioneal injection of Narcoren at a dose of ≥ 2 mL/kg bw (equivalent to 320 Mg sodium pentobarbitone/kg bw).
- The draining lymph nodes were rapidly excised and pooled for each experimental group (8 nodes/group). Single cell suspensions (phosphate buffered saline) of pooled lymph node cells were prepared by mental disaggregation through stainless steel gauze (200 µm mesh size). After washing 3 × with phosphate buffered saline (approx. 10 mL) the lymph node cells were resuspended in 5 % trichloroacetic acid (approx. 3 mL) and incubated at approx. 4 °C overnight for precipitation of macromolecules. The precipitates were then resuspended in 5 % trichloroacetic acid (1 mL) and transferred to glass scintillation vials with 10 mL of "Ultima Gold" scintillation liquid and thoroughly mixed.
- The level of ³HTdR incorporation was then measured on a β-scintillation counter. Similarly, background ³HTdR were also measured in 2 × 1 mL aliquots of 5 % trichloroacetic acid. The β-scintillation counter expresses ³HTdR incorporation as the number of radioactive disintegrations per minute (DPM).

INTERPRETATION OF RAW DATA
- The proliferative response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (DPM/node) and as the ratio of ³HTdR into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes (stimulation index, SI). Before DPM/node values were determined, mean scintillation-background DPM was subtracted from test and control raw data.
- A test item would have been regarded as a sensitiser in the LLNA if the following criteria were fulfilled:
-- First, that exposure to ≥ concentration of the test item resulted in an incorporation of ³HTdR ≥ 3 × recorded in control mice, as indicated by the stimulation index.
-- That the data are consistent with a conventional dose-response, allowing (especially at high concentrations) for either local toxicity or immunological suppression.
-- The decision to select a stimulation index of 3 an as arbitrary indication of sensitising activity was made on the basis of investigations performed with a wide range of chemicals.

OBSERVATIONS
- In addition to the sensitising reactions, the following observations were recorded during the test and observation period:
-- Mortality/viability
-- Body weights (at acclimitisation and at necropsy)
-- Clinical signs, local and systemic (daily from acclimitisation to termination, treatment sites paid particular attention).

Positive control substance(s):

mercaptobenzothiazole (CAS No 149-30-4)

Statistics:

- The mean values and standard deviations were calculated in the body weight tables
- The EC3 value was calculated according to the equation: EC3 = (a-c)((3-d)/(b-d))+c, where (a, b) and (c, d) are the co-ordinates of the two pair of data lying immediately above and below the S.I. value of 3 on the dose-response plot.

Positive control results:

1 %: 3725 DPM, SI of 1.0 (negative)
5 %: 11251 DPM, SI of 2.9 (negative)
10 %: 16792 DPM, SI of 4.4 (positive)
25 %: 24360 DPM, SI of 6.4 (positive)

Overall result positive. EC3 = 5.33 %

Parameter:

SI

Remarks on result:

other: 0 % (negative control): 0 5 %: 1.7 10 %: 5.3 25 %: 7.5 50 %: 8.7 75 %: 8.8 EC3 = 6.8 %

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: 0 % (negative control): 4146 5 %: 7028 10 %: 21816 25 %: 31132 50 %: 36016 75 %: 36335

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was assessed for skin sensitisation according to OECD guideline 429. The test material was found to be sensitising with an EC3 value of 6.8 % concentration w/v.

A valid study is available for the analogue substance, Undec-10-enal. It is a GLP compliant study conducted in compliance with agreed protocols, with no or minor deviations for the standard test. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (Dodecanal) and source substance (Undec-10-enal) and their similar physico-chemical properties.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In the absence of data on the target substance, data was presented on the analogue substance, Undec-10-enal. A study conducted according to OECD guideline 429 demonstrated that concentrations ranging from 1 to 25 % (w/v) had allergenic potential. The highest EC value obtained, 2.8 at 10 % concentration, was below the threshold of 3.0, however the value for 25 % concentration was lower (2.2). A further study was performed with concentrations ranging from 5 to 75 % (w/v) which concluded that the test material was sensitising with a calculated EC3 value of 6.8 % (w/v). Evidence of a dose-response relationship was also found, especially if the results of the two studies are considered together.

Migrated from Short description of key information:
In the absence of data on the target substance, data was presented on the analogue substance, Undec-10-enal. The test substance was sensitising to skin when assessed according to OECD guideline 429. Under the conditions of the test, the test material was found to be sensitising with an EC3 value of 6.8 % concentration w/v.

Justification for selection of skin sensitisation endpoint:
The target substance was assessed for skin sensitisation according to OECD guideline 429.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test substance was found to be sensitising according to OECD guideline 429 and should therefore be classified as a Category 1 skin sensitiser according to Annex I of 1272/2008/EC (CLP).