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Description of key information

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Skin sensitisation

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Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP.
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)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Strain: Mice, CBA/CaOlaHsd. Supplier: Harlan Winkelman GmbH, D-33176 Borchen.Sex, specification: Females, healthy young adult nulliparous animals.Age of the animals: About 8 weeks at the first administration.Weight range of the animals at the first application: 16.2 - 20.6 g.Hygiene: Optimal hygienic conditions.Room temperature: Average of 22.0 °C (continuous monitoring and recording).Relative humidity: Average of 44.4 % (continuous monitoring and recording).Light: Only artificial light from 6.00 a.m. to 6.00 p.m.Cages: Single caging. Makrolon cages type II, (22 cm x 16,5 cm ground area, 15 cm high).Feed: Altromin maintenance diet for rats and mice, item No. 1324forte, ad libitum.Random samples of the feed are analysed for contaminants.Water: Tap water offered in Makrolon-bottles with stainless steel canules, ad libitum.Bedding material: Wood chips (aspen) Fa. ABEDD Dominik Mayr KEG, A 8580 Köflach. Reduction of microorganisms by autoclaving.Acclimatisation: 6 days.Identification of the animals: By shearing a defined fur region on the back of the animal.
Vehicle:
dimethyl sulphoxide
Concentration:
Group Substances concentrationstotal amount of substance applied/animal A (low dose)0.25 % test substance0.375 mgB (mid dose)0.5 % test substance0.75 mgC (high dose)1.6 % (w/w) test substance2.4 mgK (negative control) DMSO 150 mgP (positive control) 25% HCA in AOO (v/v)37.5 mgHCA: Hexyl cinnamic aldehyde.AOO: Acetone:olive oil (4:1, v/v).
No. of animals per dose:
Number of animals: 5 animals/group:3 test substance groups,negative control group, positive control group.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Results are presented as test/control ratio (Stimulation index, SI), calculated as dpm test group/dpm negative control group.(dpm = disintegrations per minute, corrected by the subtraction of the background)A substance is regarded as a sensitiser in the LLNA if the test substance induces a 3-fold or greater increase in 3HTdR incorporation into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes, as indicated by the SI, together with the consideration of dose response.
Positive control results:
Application of 25 % HCA in AOO resulted in an Stimulation Index (SI) of 5. This result proves the sensitivity of the strain of animals used and the reliability of the experimental technique.HCA: Hexyl cinnamic aldehyde.AOO: Acetone:olive oil (4:1, v/v).
Parameter:
SI
Remarks on result:
other: The SIs of the test substance groups were between 0.9 and 1.6.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
Group dpm SInegative control 8860 1low dose 7733 0.9mid dose 8437 1.0high dose 14267 1.6positive control 44360 5.0

No abnormal behaviour or clinical signs were detected during the experiment in the animals.

No local irritations were observed at the application sites of all animals of all test substance groups A and B and the negative control group throughout the whole study.

On Days 3-5 all animals of the group C had slight erythema at the application sites and on Days 2-5 all animals of the positive control group had moderate erythema at the application sites indicating slight irritative skin reactions.

Interpretation of results:
not sensitising
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Adipic acid dihydrazide is not regarded as a sensitizer in the LLNA.
Executive summary:

The Local Lymph Node Assay was performed to evaluate a possible skin sensitising potential of Adipic acid dihydrazide according to the OECD-Guideline 429.

The SIs of the tested test substance concentrations were 0.9 (low dose), 1.0 (mid dose) and 1.6 (high dose). The positive control substance led to a stimulation index of 5.0, thus demonstrating the validity of the experiment.

According to the OECD-Guideline 429, "Skin Sensitisation": Local Lymph Node Assay", Adipic acid dihydrazide is not regarded as a sensitizer in the LLNA.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Migrated from Short description of key information:
Adipic acid dihydrazide is not regarded as a sensitizer in the LLNA, based on the low stimulation indices.

Justification for selection of skin sensitisation endpoint:
Key study.

Justification for classification or non-classification

No indications were obtained to justify a classification.

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