Registration Dossier

Administrative data

Description of key information

An in vivo skin sensitization study according to OECD 429 (LLNA) showed no skin sensitization in the read-across substance.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: 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:
guideline study with acceptable restrictions
Justification for type of information:
Data from the alternative salt form of the registered substance is used to satisfy the data requirement. Jusitifcation is attached in section 13.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
22 July 2010
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
06 July 2012
Deviations:
no
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Remarks:
/CaOlaHsd
Sex:
female
No. of animals per dose:
5
Positive control results:
Test group 3 (10 % PC)= SI 2.79
Test group 4 (25 %PC) = SI 7.84
EC3 value = 10.6%

Ear skin irritation: cut-off value of 1.1 for the ear weight index
Key result
Parameter:
SI
Value:
1.02
Variability:
0.59 - 1.47
Test group / Remarks:
1 % test item
Key result
Parameter:
SI
Value:
0.86
Variability:
0.20 - 1.43
Test group / Remarks:
2 % test item
Key result
Parameter:
SI
Value:
1.32
Variability:
0.76 - 2.00
Test group / Remarks:
5 % test item
Cellular proliferation data / Observations:
EC3 CALCULATION
The EC3 value could not be calculated, since all S.I.´s are below the threshold value of 3.

CLINICAL OBSERVATIONS:
Viability / Mortality
No deaths occurred during the study period.

Clinical signs
No signs of systemic toxicity were observed during the study period. On day 6, the animals treated with the low and high dose of the test item and some of the animals treated with the mid dose of the test item showed slightly scaly ears. Moreover, two animals of the mid dose group (animals 14 and 15) and one animal of the high dose group (animal 19) showed slight eschar formation. A possible erythema of the ear skin could not be determined in the mid and high dose group, due to the colour of the test item.

Body weights
The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

Lymph node weights and cell counts
The measured lymph node weights and –cell counts of all animals treated were recorded after sacrifice. A statistically significant or biologically relevant increase in lymph node weights or – cell counts was not observed in any of the test item treated groups in comparison to the vehicle control group. For BALB/c mice, a cut-off value for the lymph node cell count index of 1.55 was reported for a positive response. The indices determined for the lymph node cell count did not reach or exceed this threshold.

Ear weights
The measured ear weight of all animals treated was recorded on test day 6 (after necropsy). A biologically relevant or statistically significant increase in ear weights was not observed. Furthermore, the cut-off value (1.1) of the ear weight index for a positive response regarding ear skin irritation reported for BALB/c mice was not reached or exceeded in any of the treated groups.

Interpretation of results:
GHS criteria not met
Conclusions:
The registered substance is considered not skin sensitising based on an LLNA study on the read-across substance.
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

The CLP classification criteria are not met.