Registration Dossier

Administrative data

Description of key information

Based on the available in vivo test data for analogous substances which indicate an absence of skin sensitising effect, an absence of evidence from widespread consumer and occupational use of inorganic borates and very low dermal penetration, it can be concluded that dilithium tetraborate is unlikely to cause sensitisation by skin contact.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation, other
Remarks:
Weight of evidence
Type of information:
other: Weight of evidence
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline followed
Principles of method if other than guideline:
A literature review of available data which is considered relevant to dilithium tetraborate was evaluated to ascertain the potential for skin sensitisation effects.
Type of study:
other: Weight of evidence report
Other effects / acceptance of results:
This is a weight of evidence which is based on different types of data which are considered relevant to the assessment of the likelihood of skin sensitising effects to occur by exposure to dilthium tetraborate
Key result
Remarks on result:
other: Weight of evidence approach
Remarks:
This is a weight of evidence which is based on different types of data which are considered relevant to the assessment of the likelihood of skin sensitising effects to occur by exposure to dilthium tetraborate
Key result
Remarks on result:
other: Weight of evidence approach
Remarks:
This is a weight of evidence which is based on different types of data which are considered relevant to the assessment of the likelihood of skin sensitising effects to occur by exposure to dilthium tetraborate
Cellular proliferation data / Observations:
This is a weight of evidence which is based on different types of data which are considered relevant to the assessment of the likelihood of skin sensitising effects to occur by exposure to dilthium tetraborate.

A literature review of in vivo skin sensitisation test data for boric acid, disodium tetraborate anhydrous, disodium tetraborate pentahydrate and disodium tetraborate decahydrate reported no signs of skin sensitisation. (EU Risk Assessment, 2007, p.26). Based on this data the Scientific Committee on Consumer Safety (SCCS) considers these substances not to be sensitising by either skin or respiratory contact. (SCCS,2010) In addition, sodium borate also tested negative in the Buehler test (EU Risk Assessment 2007a, p85).

Dilithium tetraborate is structurally analogous to disodium tetraborate. The only difference between the two is the alkali metal (lithium rather than sodium) which is present.

Skin sensitisation results from a Buehler study (OECD TG 406) on lithium carbonate indicated that it is not sensitising by skin contact(NICNAS, 2018). It is therefore unlikely that the lithium cation of dilithium tetraborate would cause sensitisation by skin contact. Furthermore, historical evidence of extensive consumer exposure to sodium carbonate has not provided any cases of skin sensitisation. This would therefore suggest that carbonate salts of alkali metals are unlikely to be sensitisers by skin contact (Hera,2005)

There is no historical evidence of skin sensitisation in humans which have been occupationally exposed to borates (Bruze et al., 1995; NICNAS, 2018). Furthermore, a wide dispersive use of borates in consumer products (which include household cleaning products and medical care products) has also provided no evidence of skin sensitisation effects (European Union Risk Assessment Report, 2007a, p 64).

Based on existing evidence related to the very low uptake through intact skin of boron (US, EPA, 2004) and boric compounds, a dermal absorption rate of 0.5% has been put forward for risk assessment purposes (NICNAS, 2O18, SCCS, 2010, European Union Risk Assessment Report, 2007/2007a). However, it has been suggested that for borates, the absorption could be lower than 0.5%. (NICNAS, 2O18) Additionally, dermal uptake of lithium is also expected to be very low. (NICNAS, 2018).

Although Fitzpatrick et al., (2017, p.37) writes‘the critical information is an understanding of the dose that becomes available in the viable epidermis to bind covalently with skin proteins to form the immunogenic complex’, there still needs to be absorption across the stratum corneum to enable the chemical to reach the viable epidermis. In the case of borates, it is generally accepted that dermal absorption is likely to be very low (ca. 0.5% or lower), which would also be consistent with the water solubility (141.2 g/L).

Furthermore, the negative in vivo test results from the analogous substance disodium tetraborate and other borates (EU Risk Assessment, 2007, p.26) suggest either there is no bioavailability of the inorganic borates within the viable epidermis, or if the dose is available in the viable epidermis it does not covalently bind with skin proteins, or if covalent binding does occur, there is insufficient concentration to elicit the symptoms of allergy.

Dilithium tetraborate is classified as positive in the KeratinoSensTM assay (OECD TG442D) whereas calcium metaborate was classified as negative in the KeratinoSensTM assay (OECD TG442D). It is believed that neither substance is in the applicability domain of this test method and therefore both results should be discounted.

The borates are considered to be outside the applicability domain of the Keratinosens assay since this assay was validated exclusively with organic compounds (see:https://eurl-ecvam.jrc.ec.europa.eu/eurl-ecvam-recommendations/recommendation-keratinosens-skin-sensitisation). In addition, in classification schemes inorganic compounds are not included (e.g. Asturiol et al, Toxicology in vitro 2016;36:197).

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the available in vivo test data for analogous substances which indicate an absence of skin sensitising effect, an absence of evidence from widespread consumer and occupational use of inorganic borates and very low dermal penetration, it can be concluded that dilithium tetraborate is unlikely to cause sensitisation by skin contact.
Executive summary:

Based on the available in vivo test data for analogous substances which indicate an absence of skin sensitising effect, an absence of evidence from widespread consumer and occupational use of inorganic borates and very low dermal penetration, it can be concluded that dilithium tetraborate is unlikely to cause sensitisation by skin contact.

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

Based on the available in vivo test data for analogous substances which indicate an absence of skin sensitising effect, an absence of evidence from widespread consumer and occupational use of inorganic borates and very low dermal penetration, it can be concluded that dilithium tetraborate is unlikely to cause sensitisation by skin contact.