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Description of key information

Results for sensitisation were based on two UVCB substances of which the constituents show high structural similarity to the target substance (EC 943-133-8).

In an OECD 429 study, CAS 85029-58-9 was found to be sensitizing to the skin.

In an OECD 429 study, CAS 84961-40-0 was not found to be sensitizing to the skin.

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:
weight of evidence
Justification for type of information:
Please refer to chapter 13 for the read-across justification.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Parameter:
SI
Value:
2.89
Test group / Remarks:
1% in vehicle (DMF vehicle)
Remarks on result:
other: Result read-across source CAS No. 85029-58-9
Parameter:
SI
Value:
2.54
Test group / Remarks:
2.5% in vehicle (DMF vehicle)
Remarks on result:
other: Result read-across source CAS No. 85029-58-9
Key result
Parameter:
SI
Value:
4.36
Test group / Remarks:
5% in vehicle (DMF vehicle)
Remarks on result:
other: Result read-across source CAS No. 85029-58-9
Key result
Parameter:
EC3
Value:
3.1
Remarks on result:
other: Result read-across source CAS No. 85029-58-9
Parameter:
SI
Value:
1.27
Test group / Remarks:
2.5% in DMF
Remarks on result:
other: Result read-across source CAS No. 84961-40-0
Parameter:
SI
Value:
0.92
Test group / Remarks:
5% in DMF
Remarks on result:
other: Result read-across source CAS No. 84961-40-0
Parameter:
SI
Value:
1.23
Test group / Remarks:
10% in DMF
Remarks on result:
other: Result read-across source CAS No. 84961-40-0
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No substance-specific data on the acute oral toxicity of the substance (EC 943-133-8) are available. However, according to Article 13 of legislation EC1907/2006, in case no appropriate animal studies are available for assessment information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. CAS No. 85029-58-9 and CAS No. 84961-40-0 are components of the test item with high structural similarity to the target substance EC 943-133-8. Therefore, the toxicological behaviour of EC 943-133-8 is expected to be similar to that of CAS No. 85029-58-9 and CAS No. 84961-40-0.

 

The skin sensitizing potential of CAS No. 85029-58-9 and CAS No. 84961-40-0 was assessed using GLP-compliant radioactive Murine Local Lymph Node Assay, performed according to OECD guideline 429. The assay simulates the induction phase for skin sensitisation in mice. It determines the response of cells in the auricular lymph nodes to repeated application of the test substance to the dorsal skin of the ears.

CAS No. 85029-58-9

Groups of 5 female CBA/CaOlaHsd mice each were treated with 1%, 2.5% and 5% w/w preparations of the test item in N,N-Dimethylformamide (DMF) or with the vehicle alone. The high concentration was selected based on the presence of ear skin irritation in a pretest using a 10% or 50% preparation in DMF. The study used 3 test groups and 1 control group. Each test animal was treated with 25 µL per ear of the appropriate test item preparation, applied to the dorsal surfaces of both ears for three consecutive days. The control group was treated with 25 µL per ear of the vehicle alone. Three days after the last application the mice were injected into the tail vein with 20 µCi of 3H-thymidine in 250 µL of sterile saline. About 5 hours after the 3H-thymidine injection, the mice were sacrificed and the auricular lymph nodes were removed. Lymph node response was evaluated by measuring 3H-thymidine incorporation (indicator of cell proliferation). Cell counts and weights of each animal’s pooled lymph nodes were also determined. In addition, a 0.8 cm diameter sample was punched out of the apical part of each ear and for each animal the weight of the pooled punches was determined in order to obtain an indication of possible skin irritation. No signs of systemic toxicity were noticed in all animals during general observation. When applied as 5% preparation in DMF, the test substance induced a statistically significant increase of 3H-thymidine incorporation into the cells from the auricular lymph nodes, which was above the cut off value for biological relevance(increase above the cut off stimulation index (SI) of 3). The increases of the 2.5% and 1% test-substance preparations were statistically significant, but failed to reach the cut off. In addition, there was no relevant increase in lymph node weights without concentration dependence, as well. The test-substance preparations did not cause relevant increases in ear weights demonstrating the absence of ear skin irritation. Based on the available information, the test item exhibits skin sensitising potential under the selected test conditions. The EC3 value was calculated to be 3.1%.

 

CAS No. 84961-40-0

Groups of 5 female CBA/CaOlaHsd mice each were treated with 2.5%, 5% and 10% w/w preparations of the test substance in dimethylformamide (DMF) or with the vehicle alone. The high concentration was selected based on the presence of systemic toxicity in a pretest using 50% and 25% test substance preparations in dimethylformamide (DMF). The study used 3 test groups and 1 control group. Each test animal was treated with 25 μL per ear of the appropriate test-substance preparation, applied to the dorsal surfaces of both ears for three consecutive days. The control group was treated with 25 μL per ear of the vehicle alone. Three days after the last application the mice were injected into the tail vein with 20 μCi of 3H- thymidine in 250 μL of sterile saline. About 5 hours after the 3H-thymidine injection, the mice were sacrificed and the auricular lymph nodes were removed. Lymph node response was evaluated by measuring 3H-thymidine incorporation (indicator of cell proliferation). Cell counts and weights of each animal’s pooled lymph nodes were also determined. In addition, a 0.8 cm diameter sample was punched out of the apical part of each ear and for each animal the weight of the pooled punches was determined in order to obtain an indication of possible skin irritation. No relevant signs of systemic toxicity were noticed in all animals during general observation. However, the mean body weight of test group 4 (10% concentration) decreased over the study period. When applied as 2.5%, 5% and 10% preparations in DMF, the test substance did not induce a biologically relevant (no increase above the cut off Stimulation Index of 3) or statistically significant increase of 3H-thymidine incorporation into the cells from the auricular lymph nodes. Concomitantly, there were no biologically relevant or statistically significant increases in lymph node cell counts (no increase to 1.5-fold or above of control value = stimulation index (SI) ≥ 1.5) at all concentrations. There were no increases in lymph node weights at all concentrations as well. The ear weights of all test-substance treated animals were not relevantly elevated as compared to the vehicle control group demonstrating the absence of ear skin irritation. Red discoloration of the ear skin of the test-substance treated animals was noted from study day 1 up to study day 5. In addition, encrusted compound residues (slight to severe) around the application site were observed in all test-substance treated animals on study day 5. The animals of the vehicle control group showed slight scaling on study day 5. Thus, it is concluded that CAS No. 84961-40-0 does not exhibit a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the EC3 value derived in the LLNA the substance has to be classified as Skin Sens. 1B, H317 (May cause an allergic skin reaction), in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.