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Toxicological information

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Description of key information

A GPMT study with substance analogue Tributylmethylammoniummethylsulfate is available, performed according to OECD/EC test guidelines and GLP principles. No skin reactions were observed after the challenge and Tributylmethylammoniummethylsulfate was considered not to be a skin sensitiser. An LLNA skin sensitisation study with substance analogue TMAC is available, performed according to OECD/EC test guidelines. As the SI appeared not to be ≥ 3 when tested up to 10%, TMAC is not considered to be a skin sensitiser. Based on the data of these analogues, MTBAC is considered not to have sensitising properties.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in section 13.
Reason / purpose:
read-across source
GLP compliance:
yes
Key result
Parameter:
SI
Remarks:
0%
Value:
0.5
Variability:
± 0.2
Test group / Remarks:
Animals tested at 25% were sacrificed for ethical reasons.
Key result
Parameter:
SI
Remarks:
5%
Value:
0.5
Variability:
± 0.2
Key result
Parameter:
SI
Remarks:
10%
Value:
1.1
Variability:
± 0.3
Cellular proliferation data / Observations:
Two animals at 25% were sacrificed for ethical reasons on days 3 or 4, respectively. Clinical signs noted for both of these animals included flat posture, ptosis, tremors and/or irregular breathing on day 3. One of the surviving animal showed tremors and abnormal gait on day 3.
 
The body weight loss noted for some of the surviving animals across the dose groups was considered not toxicologically significant since the changes were slight in nature and no concentration-related incidence was apparent.
No irritation of the ears was observed in any of the animals examined.
The auricular lymph nodes of all (surviving) animals treated with a 10% and 25% test substance concentration appeared larger in size when compared to the other treated groups. All auricular lymph nodes of the animals of the control animals and animals at a 5% test substance concentration were considered normal in size. No macroscopic abnormalities of the surrounding area were noted in any of the surviving animals.
Interpretation of results:
GHS criteria not met
Conclusions:
In an LLNA skin sensitisation study, performed according to OECD/EC test guidelines, TMAC was considered not to be a skin sensitiser, as the SI appeared not to be ≥ 3 when tested up to 10%. Based on the data of the analogue, MTBAC is considered not to have sensitising properties.
Executive summary:

An LLNA skin sensitisation assay was performed according to OECD/EC guidelines and GLP principles with TMAC. The test substance was applied at concentrations of 5, 10 or 25%, however two of the three animals in the highest exposure group had to be sacrificed due to severe systemic toxicity. Data obtained at this concentration were not used for interpretation.

In the other groups, no significant body weight loss was noted, and no irritation of the ears was observed. The auricular lymph nodes of all (surviving) animals treated with a 10% and 25% test substance concentration appeared larger in size when compared to the other treated groups, the auricular lymph nodes of animals at 5% test substance concentration were considered normal in size. The SI values calculated for the substance concentrations 5 and 10% were 0.5 and 1.1 respectively. Based on these data, TMAC is considered not to be a skin sensitizer. These data were read across to MTBAC and therefore MTBAC is not considered to have skin sensitising properties.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
For Read Across Justification please refer to Section 13.
Reason / purpose:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Executive summary:

A Maximization Test was performed in 10 female guinea pigs (Pirbright White, Dunkin Hartley) according to OECD guideline 406 and in compliance with GLP. The intradermal induction caused moderate and confluent erythema and swelling at the injection sites of all control group animals and all test group animals at which only Freund's adjuvant 0.9% aqueous NaCl-solution (1:1) was applied. Injections of 5% test substance preparations in 0.9% aqueous NaCl-solution or in Freund's adjuvant / 0.9% aqueous NaCl-solution (1:1) caused moderate and confluent erythema and swelling in all test group animals. The injection sites of all control group animals, at which 0.9% aqueous NaCl-solution was applied, did not show any skin reactions. The 50% preparation of 0.9% aqueous NaCl-solution with Freund's adjuvant / 0.9% aqueous NaCl-solution (1:1) caused moderate and confluent erythema and swelling in all control group animals. After the percutaneous induction with a 50% test substance preparation incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test group animals. The challenge with the 25% test substance preparation in did not cause any skin reactions, neither in control group nor in the test group 24 and 48 hours after removal of the patches. The results of this study show that 1 -butanaminium, N,N-dibutyl-N-methyl-, methyl sulfate does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen. These data were read across to MTBAC and therefore MTBAC is not considered to have skin sensitising properties.

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

A Maximization Test was performed in 10 female guinea pigs (Pirbright White, Dunkin Hartley) according to OECD guideline 406 and in compliance with GLP. The intradermal induction caused moderate and confluent erythema and swelling at the injection sites of all control group animals and all test group animals at which only Freund's adjuvant 0.9% aqueous NaCl-solution (1:1) was applied. Injections of 5% test substance preparations in 0.9% aqueous NaCl-solution or in Freund's adjuvant / 0.9% aqueous NaCl-solution (1:1) caused moderate and confluent erythema and swelling in all test group animals. The injection sites of all control group animals, at which 0.9% aqueous NaCl-solution was applied, did not show any skin reactions. The 50% preparation of 0.9% aqueous NaCl-solution with Freund's adjuvant / 0.9% aqueous NaCl-solution (1:1) caused moderate and confluent erythema and swelling in all control group animals. After the percutaneous induction with a 50% test substance preparation incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test group animals. The challenge with the 25% test substance preparation in did not cause any skin reactions, neither in control group nor in the test group 24 and 48 hours after removal of the patches. The results of this study show that 1 -butanaminium, N,N-dibutyl-N-methyl-, methyl sulfate does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

An LLNA skin sensitisation assay was performed according to OECD/EC guidelines and GLP principles. Tetramethylammonium chloride was applied at concentrations of 5, 10 or 25%, however two of the three animals in the highest exposure group had to be sacrificed due to severe systemic toxicity. Data obtained at this concentration were not used for interpretation. In the other groups, no significant body weight loss was noted, and no irritation of the ears was observed. The auricular lymph nodes of all (surviving) animals treated with a 10% and 25% test substance concentration appeared larger in size when compared to the other treated groups, the auricular lymph nodes of animals at 5% test substance concentration were considered normal in size. The SI values calculated for the substance concentrations 5 and 10% were 0.5 and 1.1 respectively. Based on these data, TMAC is considered not to be a skin sensitizer.

The rationale to read across these data to MTBAC is attached in section 13.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, MTBAC is not classified for skin sensitization according to CLP Regulation (EC) No. 1272/2008.