Registration Dossier

Administrative data

Description of key information

Read across: WoE, ZnSO4, LLNA (no guideline, no GLP), negative (Basketter et al. 1999, Ikarashi et al. 1992)

Read across: WoE, FF6, GPMT (OECD 406, GLP), FF6, negative (Frosch 1998)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reason / purpose:
read-across source
Reason / purpose:
assessment report
Positive control results:
80 % of the animals used reacted with skin sensitisation and the skin-fold thickness was significantly increased in the treated animals on days 23 and 24. The positive control results demonstrate that the laboratory has the capability to identify positive dermal sensitizers.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
75:25 (w/w) mixture of test article with white vaseline
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no skin reaction
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
75:25 (w/w) mixture of test article with white vaseline
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no skin reaction
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reaction
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reaction
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10% solution in liquid paraffin
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
increased skin-fold thickness
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
10% solution in liquid paraffin
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
increased skin-fold thickness
Interpretation of results:
GHS criteria not met
Conclusions:
Brüggolit FF6 has no skin sensitisation effect.
Executive summary:

The skin sensitisation potential of the test article was investigated in the Guinea-pig Maximisation Test with the Dunkin Hartley albino strain following OECD 406 and GLP criteria. The sensitivity of the test animals to benzocaine has been demonstrated. In the course of testing, no clinical signs were observed and the body weight gain of animals was not significantly influenced. The choice of doses was based on the results ofthe pilot study. The animals showed a very homogeneous reaction to the application of the test substance. The intradermal injection of the 10 % solution of the test article alone and in combination with sensitisation potentiating FCA lead to slight erythema and oedema. The same pattern was seen at injection site 1 (FCA/water mixture ) in the control animals. Topical induction was attempted with the 75:25 mixture of test article with white vaseline on day 7. After removal of the occlusive dressing on day 9 not any skin irritation was recorded in the animals. After challenge with the 75:25 preparation in white vaseline neither the control nor the dose group animals showed any skin effects. Oedema formation was excluded by measurement of skin-fold thickness. The source substance contains the major organic moieties (hydroxysulfi(o)natoacetates) that are identical to the target substance. Therefore, this study shows that no skin sensitisation potential can be attributed to the hydroxysulfi(o)natoacetate moieties of the target substance TP 1646.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reason / purpose:
read-across source
Reason / purpose:
assessment report
Parameter:
SI
Value:
2.3
Test group / Remarks:
25 % dose group
Remarks on result:
other:
Remarks:
Zinc did not stimulate lymph node cell proliferation at least threefold greater than that observed in concurrent vehicle-treated control and therefore was judged to be negative. Stimulation index (SI) was as follows: 5.0 % : 1.3; 10.0 %: 2.0; 25.0 %: 2.3. With Zn, there was a slight suggestion of a dose-response trend, but even at 25% (the highest concentration at which it was possible to test), the stimulation index reached only 2.3, and so it was recorded as negative.
Parameter:
SI
Value:
2
Test group / Remarks:
10 % dose group
Remarks on result:
other:
Remarks:
Zinc did not stimulate lymph node cell proliferation at least threefold greater than that observed in concurrent vehicle-treated control and therefore was judged to be negative. Stimulation index (SI) was as follows: 5.0 % : 1.3; 10.0 %: 2.0; 25.0 %: 2.3. With Zn, there was a slight suggestion of a dose-response trend, but even at 25% (the highest concentration at which it was possible to test), the stimulation index reached only 2.3, and so it was recorded as negative.
Parameter:
SI
Value:
1.3
Test group / Remarks:
5 % dose group
Remarks on result:
other:
Remarks:
Zinc did not stimulate lymph node cell proliferation at least threefold greater than that observed in concurrent vehicle-treated control and therefore was judged to be negative. Stimulation index (SI) was as follows: 5.0 % : 1.3; 10.0 %: 2.0; 25.0 %: 2.3. With Zn, there was a slight suggestion of a dose-response trend, but even at 25% (the highest concentration at which it was possible to test), the stimulation index reached only 2.3, and so it was recorded as negative.
Interpretation of results:
not sensitising
Conclusions:
Zn was not considered to possess, to any significant degree, the ability to cause skin sensitisation in humans, and, thus, would not be classified and labeled as sensitiser. Due to the fact that the Zn ion is the toxicological relevant moiety of TP 1646, the target substance TP 1646 is expected to be also negative in LLNA.
Executive summary:

The LLNA was used to determinethe skin sensitization potential of 13 metal salts. With Zn, there was a slight suggestion of a dose-response trend, but even at 25% (the highest concentration at which it was possible to test), the stimulation index reached only 2.3, and so it was recorded as negative. In conclusion, Zn was not considered to possess the ability to cause skin sensitisation in humans, and, thus, would not be classified and labeled as sensitiser.

Due to the fact that the Zn ion is the toxicological relevant moiety of TP 1646, the target substance TP 1646 is expected to be also negative in LLNA.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reason / purpose:
read-across source
Reason / purpose:
assessment report
Parameter:
SI
Remarks:
zinc sulphate
Value:
1.41
Test group / Remarks:
concentration 1: 10 %
Parameter:
other: disintegrations per minute (DPM)
Remarks:
zinc sulphate
Remarks on result:
other: Mean counts per minute ± SD (x 10E-3): 2.14 ± 0.77
Parameter:
SI
Value:
2.32
Test group / Remarks:
positive control
Parameter:
SI
Test group / Remarks:
concentration 2
Remarks on result:
not measured/tested
Parameter:
SI
Test group / Remarks:
concentration 3
Remarks on result:
not measured/tested
Interpretation of results:
GHS criteria not met
Conclusions:
Although there are some deficiencies in the test conduction, the stimulation index was determined to be 1.41 (mean cpm is even below the mean cpm of the vehicle). Therefore, Zn is not sensitising. Due to the fact that the Zn ion is the toxicological relevant moiety of TP 1646, the target substance TP 1646 is expected to be also negative in LLNA.
Executive summary:

In a dermal sensitisation study with Zinc sulphate heptahydrate in 20% ethanol solution, 6-8 week old female Balb/c mice (three animals / dose) were tested in the murine local lymph node assay. The test substance was applied on three consecutive days on the dorsum of each ear, local lymph nodes were isolated on fourth day after application. Isolated cells were cultivated with [3H]methyl thymidine ([3H]TdR) and [3H]TdR incorporation was measured with a scintillation counter. The stimulation index (SI) for ZnSO4 was determined to be 1.41 (SI < 2), showing no significant increase in lymphocyte proliferation compared to vehicle alone. In this study, ZnSO4 is not a dermal sensitiser. This study is considered to be reliable and to fulfill general scientific requirements.

Due to the fact that the Zn ion is the toxicological relevant moiety of TP 1646, the target substance TP 1646 is expected to be also negative in LLNA.

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

GPMT (OECD 406, GLP), Frosch 1998

The skin sensitisation potential of the test article was investigated in the Guinea-pig Maximisation Test with the Dunkin Hartley albino strain following OECD 406 and GLP criteria. The sensitivity of the test animals to benzocaine has been demonstrated. In the course of testing, no clinical signs were observed and the body weight gain of animals was not significantly influenced. The choice of doses was based on the results ofthe pilot study. The animals showed a very homogeneous reaction to the application of the test substance. The intradermal injection of the 10 % solution of the test article alone and in combination with sensitisation potentiating FCA lead to slight erythema and oedema. The same pattern was seen at injection site 1 (FCA/water mixture ) in the control animals. Topical induction was attempted with the 75:25 mixture of test article with white vaseline on day 7. After removal of the occlusive dressing on day 9 not any skin irritation was recorded in the animals. After challenge with the 75:25 preparation in white vaseline neither the control nor the dose group animals showed any skin effects. Oedema formation was excluded by measurement of skin-fold thickness. The source substance contains the major organic moieties (hydroxysulfi(o)natoacetates) that are identical to the target substance. Therefore, this study shows that no skin sensitisation potential can be attributed to the hydroxysulfi(o)natoacetate moieties of the target substance TP 1646.

LLNA, Basketter 1998, Ikarashi 1992

The LLNA was used to determinethe skin sensitisation potential of ZnSO4. In both studies Zn was not considered to possess the ability to cause skin sensitisation in humans, and, thus, would not be classified and labeled as sensitiser.

Due to the fact that the Zn ion is the toxicological relevant moiety of TP 1646, the target substance TP 1646 is expected to be also negative in LLNA.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results for the source substances the target substance is not classified according to Regulation (EC) No 1272/2008.