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Administrative data

Description of key information

not sensitizer

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation, other
Remarks:
in vivo LLNA
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: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Justification for type of information:
Justification for read across is detailed in the report attached to the IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
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:
other: BALB/CBYJICO
Sex:
female
Details on test animals and environmental conditions:
Source: Breeding farm VELAZ s.r.o., Lysolajské údolí 15/53, 165 00 Prague 6, Czech Republic, RČH CZ 11760500
Number of animals:
Pilot experiment – 3 females
group: Exposed groups – 15 females (5 animals in three groups)
Positive control group – 5 females
Negative control group – 5 females
Total: 28 animals
Age: 8 to 10 weeks (at start of dosing)
Body weight range: 14.78 - 18.67 g (at start of dosing), in pilot experiment 14.96 - 17.59 g
Health examination: All animals were examined during the acclimatisation period
Acclimatisation: 7 days

Animal rooms: Monitored conditions, microbiologically defined background, according to internal SOP No.40
Room temperature: 22 ± 3 °C, permanently monitored
Relative humidity: 30 – 70 %, permanently monitored
Light: 12 hours light/dark cycle: 6am-6pm/6pm-6am
Animal caging: Animals in groups in macrolon cages with sterilized softwood shavings
Water: Drinking tap water ad libitum. Water quality corresponded to Regulation No. 252/2004 Czech Coll. Of Law, Health Ministry
Diet: Pelleted standard diet for experimental animals ad libitum (Altromin, manufacturer: Altromin Spezialfutter GmbH & Co. KG, Germany).
Microbiological control and content of nutrients is performed according internal SOP No. 72.
Cleaning and disinfection of animal room was regularly performed, as it is described in internal SOP No.10.
Positive control results:
The positive control item Dinitrochlorobenzene (DNCB) as a contact allergen (concentration 0.5% (w/v) elicited the expected reaction pattern with significant increase in Stimulation Index of cell proliferation and of ear weight.
Parameter:
SI
Value:
0.68
Test group / Remarks:
dose 50%
Parameter:
SI
Value:
0.85
Test group / Remarks:
dose 5%
Parameter:
SI
Value:
0.66
Test group / Remarks:
dose 0.5 %
Parameter:
other: disintegrations per minute (DPM)
Value:
279.31
Test group / Remarks:
dose 50%
Parameter:
other: disintegrations per minute (DPM)
Value:
422.65
Test group / Remarks:
dose 5 %
Parameter:
other: disintegrations per minute (DPM)
Value:
250.45
Test group / Remarks:
dose 0.5%

Main test:

Body Weight of Animals: Individual body weight of females before administration and before necropsy was relatively well balanced (result of random selection of animals into groups). Very slight reduction of body weight (in tenths of grams) was recorded only in one animal at the middle dose level. Body weight increment was calculated from values of day 6 just before necropsy and day 1 before first application. Body weight increment was lower in treated group at the middle dose level.

Mortality, Clinical Observations No animal died during the main study. No symptoms of toxicity and no erythema on application site were observed in all animals from the negative control group and all animals administered by the test substance. All animals in the positive control group showed symptoms caused by the application of DNCB: hyperaemia of skin with well defined erythema (see tab. No. 8) on application site, clonospasm and increased response to stimuli.

Cell Proliferation The value of DPM and SI for positive control group was increased. The SI was ≥ 3 (7.18) – the LLNA was efficient (see Table 9). The SI for the test groups treated by the test substance at the all dose levels was below the threshold, stimulation index (SI) is < 3.

Irritating Effect of the Test Substance:

In the positive control group, the weight of ear target was significantly increased against negative control group. No erythema of skin was observed during the clinical observation at all dose levels. Statistically significant increase of ear weight was recorded at the middle dose level. Residues of the test substance on the ears were visible during whole study so it could cause this weight increase.

Interpretation of results:
GHS criteria not met
Conclusions:
Not sensitizer for skin
Executive summary:

Under the given test conditions, the animals exposed to the test substance does not elicit sensitising response in LLNA assay.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Under the given test conditions, the animals exposed to the test substance does not elicit sensitising response in LLNA assay.

Negative results in cell proliferation revealed that the test substance could not be a contact allergen in mice.

The test substance provides negative sensitising response in LLNA.

The substance could be considered as not sensitizer and does not required any classification.

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