Manganese antimony titanium buff rutile

Endpoint summary

Description of key information

Skin sensitisation: not sensitising (equivalent or similar to OECD guideline 429)

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

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogy in structure, physico-chemical properties as well as the behaviour in the bioaccessability studies indicate that all three rutiles are of low bioavailability after dermal exposure. The higher release of manganese in artificial sweat solution from Manganese antimony titanium buff rutile is not considered relevant as soluble manganese ions are not known for a skin sensitising potential. All three rutiles do not show an irritation potential when applied onto skin (or into eyes).

Thus, based on the above-mentioned similarities the read across for the endpoint skin sensitization from Chrome antimony titanium buff rutile and Chrome tungsten titanium buff rutile to Manganese antimony titanium buff rutile is considered to be acceptable.

See read-across justification attached to IUCLID section 13.2

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

10%

Key result

Parameter:

SI

Value:

1.69

Test group / Remarks:

25%

Key result

Parameter:

SI

Value:

1.2

Test group / Remarks:

50%

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

An in vivo skin sensitisation study (local lymph node assay (LLNA); OECD 429 (modified)) with manganese antimony titanium buff rutile was conducted (Haferkorn, 2022). Groups of 6 female NMRI mice were treated with 10, 25 and 50 % of the substance in propylene glycol. Signs of skin sensitisation but no irritation potential were noted for the highest test concentration of 50 % (w/w) test item. However, the findings in this local lymph node assay are considered to be inconclusive for the following reasons:

The results of the positive control group did unexpectedly reveal a skin irritant potential instead of a skin sensitisation potential. Therefore, a reference to the historical background data of the positive control item (35 studies performed between years 2017 and 2019) was made by the laboratory. It was argued that the positive control item is not mandatory (not included in the acceptance criteria of this test according to OECD 429). However, even the positive control is not mandatory, failure of a positive control that is run concurrently in a study should not occur, when the test substance give positive results. In addition, the OECD guideline 429 (2010) recommends the inclusion of a concurrent positive control, but also foresees the possibility of periodic testing: “While inclusion of a concurrent PC group is recommended, there may be situations in which periodic testing (i.e. at intervals ≤ 6 months) of the PC test substance may be adequate for laboratories that conduct the LLNA regularly (i.e. conduct the LLNA at a frequency of no less than once per month) and have an established historical PC database that demonstrates the laboratory’s ability to obtain reproducible and accurate results with PCs.” These conditions have not been accredited in the provided historical control data. In conclusion, the integrity of the study has been questioned, since the positive control group failed, and the validity of the periodic historical control data is not demonstrated.

The data of the lymph node cell count of the vehicle control group (propylene glycol) to which the test item groups are compared shows a high relative standard deviation of 44 %. This relative standard deviation is the highest standard deviation obtained in the current study. The relative standard deviation of the vehicle control group (acetone/olive oil; rel. standard deviation: 23 %) to which the positive control group is compared is lower as well as the relative standard deviation of the historical control data (rel. standard deviation: 29 %). However,  the historical control data for controls combined all vehicles ((acetone/olive oil (4:1, v/v), N,N-dimethylformamide, propylene glycol and dimethyl sulfoxide) used by the laboratory in 35 studies conducted in the years 2017 - 2019. This implies that the controls are interchangeable.  Therefore, if the vehicle group (acetone/olive oil (4:1, v/v)) would be used to calculate the stimulation index of the high dose group (50 % concentration of manganese antimony titanium buff rutile), a stimulation index of 1.23 would be obtained instead of 1.7, which indicate no skin sensitisation potential.

Lastly, reviewing the data for lymph node weight of the test item vehicle control group (propylene glycol), it can be observed that half of the values as well as the mean value were above the values of the historical control data. The mean value was even statistically significantly higher than the historical control data.

Overall, these data suggest that the results of the vehicle control group of the test item are unreliable and unsuitable for estimating stimulation index. Consequently, the stimulation index of 1.7 for the high dose group (50% (w/w) test item) is highly questionable and offers low reliability.

Furthermore, there is no evidence in the open literature for any of the elements included in the test substance to be a skin sensitizer. A bioaccessibility study with manganese antimony titanium buff rutile in artificial sweat indicated that the element, which is mostly released from this compound, is manganese. The remaining elements (antimony and titanium) were below the limit of quantification.

Two references obtained during a literature search described local lymph node assays conducted with manganese chloride and manganese chloride tetrahydrate. These references were considered to be reliable and are summarised below:

Basketter et al. (1999) investigated the skin sensitisation potential of manganese chloride in groups of 4 CBA/CA mice using the local lymph node assay (LLNA). For application the following concentrations were used: 5.0, 10.0 and 25.0 % in petrolatum. Manganese chloride did not give rise to an increase in proliferation of lymph node cells and, therefore, was judged to have no skin sensitisation potential.

Furthermore, Ikarashi et al. (1992) investigated manganese chloride tetrahydrate for its potential to cause skin sensitisation using the local lmph node assay. Groups of 3 female Balb/c mice were treated with 10 % of the substance in 20 % ethanol on the dorsum of each ear. The surface of each ear was gently abraded prior to application. The mice exposed to the substance did not show an increase in lymph node cell proliferation compared with those exposed to vehicle alone. Therefore, manganese chloride tetrahydrate was not considered to be a skin sensitiser.

Lastly, a false positive reaction to skin sensitisation test can be assumed if a test substance does not have a structural alert. For the manganese antimony titanium buff rutile no structural alert exists.

In conclusion, based on the arguments present above this local lymph node assay with manganese antimony titanium buff rutile is considered to be inconclusive.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Manganese antimony titanium buff rutile does not possess a skin sensitisation potential and does not require classification as skin sensitiser according to Regulation (EC) No. 1272/2008 and subsequent adaptations.