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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-01-16 to 2007-02-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study. GLP.
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
adopted 24 April 2002
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-8 weeks (beginning of acclimatisation)
- Weight at study initiation: 18.4 g ±0.7
- Housing: single, Makrolon Type I, with wire mesh top (EHRET GmbH, D-79302 Emmendingen), granulated soft wood bedding (Harlan Winkelmann GmbH, D-33178 Borchen)
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum (Harlan Winkelmann GmbH, D-33178 Borchen)
- Water (e.g. ad libitum): tap water, ad libitum (Gemeindewerke, D-64380 Rossdorf)
- Acclimation period: not given

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-72%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES (GLP Main Experiment): From: 2007-01-31 To: 2007-02-06
Vehicle:
dimethylformamide
Concentration:

- non-GLP Pretest (test substance): 12.5% (w/v), 25% (w/v), 50%(w/v) and 100% (w/v)
- Main study (test substance): 25% (w/v); 50% (w/v) and 100% (w/v)
- Positive control: α-Hexylcinnamaldehyde in acetone: olive oil (4+1) at conc. 5% (w/v), 10% (w/v) and 25% (w/v)
- Negative control: equivalent volume of vehicle (dimethylformamide)
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Irritation: In a non-GLP conform pre-test in two mice, test item concentrations of 12.5%, 15%, 50% and 100% were tested on one ear each. No irritation effects were observed at these concentrations after a single application.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA (OECD 429, 24 April 2002)
- Criteria used to consider a positive response: The test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentration resulted in a 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.).

TREATMENT PREPARATION AND ADMINISTRATION:
Application: topical (epidermal) application to the dorsal surface of each ear lobe (left and right) once daily on three consecutive days with different test item concentrations of 25, 50 and 100% (w/v) in dimethylformamide. The application volume (25 µL) was spread over the entire dorsal surface (approx. diameter of 8 mm). The control animals were treated with an equivalent volume of vehicle alone.
Administration of 3H-Methyl Thymidine: 250 µL of 81.0 µCi/mL 3HTdR (corresponds to 20.3 µCi 3HTdR per mouse) by intravenous injection via a tail vein five days after the first topical application.
Determination of incorporated 3HTdR: All mice were euthanized approx. 5 hours after treatment with 3HTdR. The draining lymph nodes were excised and pooled per group (8 nodes per group). Single cell suspension of pooled lymph node cells were prepared. After resuspension in 5% trichloroacetic acid and mixing with scintillation liquid, the level of 3HTdR incorporation was measured on a β-scintillation counter. Background 3HTdR levels were measured in two 1 mL-aliquots of 5% trichloroacetic acid.
The proliverative response of lymph node cells is expressed as disintegrations per minute per lymph node (DPM/node) and as the ratio of 3HTdR incorporated into lymph node cells relative to that recoreded for control lymph nodes (stimulation index).
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
The positive control test item resulted in a stimulation index of 2.04 at 5% (w/v) and S.I.=6.31 at 10%, respectively. Accordingly, the EC3 was calculated to 6.1% and thus indicated the adequate function of the test system.
Parameter:
SI
Remarks on result:
other: Test substance: 25% (w/v): S.I. = 0.69 50% (w/v): S.I. = 0.56 100% (w/v): S.I. = 0.59 The EC3 value could not be calculated, since all S.I.s are below 3.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Control group: 407.8 DPM/lymph node (3262.0 total DPM) Test substance: 25% (w/v): 280.6 DPM/lymph node (2245.0 total DPM) 50% (w/v): 229.0 DPM/lymph node (1832.2 total DPM) 100% (w/v): 239.3 DPM/lymph node (1914.6 total DPM)

MAIN STUDY

No deaths, no symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period. Body weights of the test animals, which were recorded prior to the first application and prior to treatment with 3HTdR, were within the range commonly recorded for animals of this strain and age (only three mice lost 0.1-1.7 g of their initial weight).

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this Local Lymph Node Assay, MAPTAC (50% solution in water) was not identified to be a dermal sensitiser.
Executive summary:

In a dermal sensitization study with the test substance MAPTAC (49.8% solution in water) in Dimethylformamide, groups of 4 female CBA/CaOlaHsd mice were tested using the LLNA method according to the OECD Guideline 429, 24 April 2002. Proliferation response of lymph node cells was measured by DPM counting of incorporated 3HTdR.

A substance is regarded as dermally sensitising if the S.I. ≥ 3.

STIMULATION INDICES (S.I.) of 0.69, 0.56 and 0.59 were determined for the test substance at concentrations of 25%, 50% and 100%, respectively in Dimethylformamide (w/v). The positive control (α-Hexylcinnamaldehyde) gave the appropriate response (EC3=6.1% in acetone:olive oil (4+1, w/v)).

In this study, MAPTAC (49.8% solution in water) is not a dermal sensitiser.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A reliable (RL=1), relevant and adequate study to assess the skin sensitisation potential of MAPTAC is available:

In a dermal sensitisation study with the test substance MAPTAC (49.8% solution in water) in Dimethylformamide, groups of 4 female CBA/CaOlaHsd mice were tested using the LLNA method according to the OECD Guideline 429, 24 April 2002. Proliferation response of lymph node cells was measured by DPM counting of incorporated 3HTdR.

A substance is regarded as dermally sensitising if the S.I. ≥ 3.

Stimulation indices (S.I.) of 0.69, 0.56 and 0.59 were determined for the test substance at concentrations of 25%, 50% and 100%, respectively in Dimethylformamide (w/v). The positive control (α-Hexylcinnamaldehyde) gave the appropriate response (EC3=6.1% in acetone:olive oil (4+1, w/v)).

In this study, MAPTAC (49.8% solution in water) is not a dermal sensitiser.

There is no information available for respiratory sensitisation. Due to the negligible vapour pressure of MAPTAC and the absence of spray applications, any respiratory hazard is not to expect.

No human information is available for skin sensitisation. However, there is no reason to believe that these results would not be applicable to humans.


Migrated from Short description of key information:
Local Lymph Node Assay: not sensitising; OECD guideline 429; GLP; Stimulation indices were 0.69, 0.56 and 0.59 at concentrations of 25%, 50% and 100% in Dimethylformamide

Justification for selection of skin sensitisation endpoint:
OECD guideline study, no deviations, GLP

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Justification for selection of respiratory sensitisation endpoint:
Inhalation is no relevant route of exposure.

Justification for classification or non-classification

Based on the available data, MAPTAC does not need to be classified for skin sensitisation according to the criteria given in regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.