Naphthenic acids, bismuth salts

Endpoint summary

Description of key information

The source substance naphthenic acids has been investigated for skin sensitisation properties in an in vivo OECD 406 Guinea pig maximisation test (Yamato et al., 2006). The results did indicate that naphthenic acids were positive in the guinea pig maximisation test.

Thus, it can be concluded, that although the bismuth(III) cation will not cause skin sensitisation, the naphthenic acids are considered skin sensitising. Taking into account that naphthenic acids, bismuth salts are manufactured with a slight excess of naphthenic acids (to ensure tri-substitution), excess naphthenic acids will be present in the UVCB substance and thus the target substance naphthenic acids, bismuth salts is considered being a skin sensitiser, accordingly.

Considering the low vapour pressure (< 1 Pa) of the substance and its use in heavy duty industrial grease, not applied as aerosols, respiratory sensitisation is not considered critical due to lack of exposure routes.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

read across from GPMT and LLNA study

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

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The substance naphthenic acids, bismuth salts is manufactured from bismuth oxide/hydroxide and 3 equivalents of naphthenic acids, resulting in the bismuth tri-naphthenate. Thus, to assess skin sensitisation properties, results for bismuth 3+ cations were assessed as well as data for naphthenic acids, the two potential hydrolysis products of the substance. The undissociated substance is considered uncritical, as its molecular mass of ~850 Dalton makes it unlikely that such compounds efficiently pass biological membranes or skin. Thus, the skin sensitisation potential of naphthenic acids, bismuth salts will be dominated by its ions, derived from hydrolysis upon contact with moist skin. In addition, pH effects are considered uncritical as naphthenic acids being typically weak acids and bismuth hydroxide, a weak base do form almost neutral neutralisation products, thus not affecting the skin barrier via pH effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source compound naphthenic acids is the starting material for the manufacturing of naphthenic acids, bismuth salts. Naphthenic acids do contain mainly hydrocarbon acids with a carbon range from 10 - 15 (other naphthenic acids may have wider ranges), with a variable number of cyclics contained (n = 0, 1, 2 and rarely 3). To a minor extent also aliphatics may be present as minor "impurities".
The naphthenic acids are reacted in a slight excess of >3 equivalents of naphthenic acids with bismuth oxide to derive naphthenic acids, bismuth salts with a slight excess of naphthenic acids, the target substance. Thus, the starting compound for the synthesis of the target compound is actually the source substance. Whereas the bismuth oxide used has a purity of 99% by weight typically, not capable of passing the human skin, the naphthenic acids, being a UVCB-type substance, are of 100% purity, by definition.
To assess the skin sensitisation potential of bismuth compounds, a soluble form, namely bismuth hydroxy nitrate oxide, has been tested in a LLNA study for skin sensitisation properties and was found negative, proving that even elevated amounts of Bi(III) cations are not capable of causing skin sensitisation.

3. ANALOGUE APPROACH JUSTIFICATION
The target substance naphthenic acids, bismuth salts, containing mainly bismuth tris-naphthenate, has a huge molecular weight (~ 850 Dalton) and it is known that such substance can hardly pass human skin, causing irritation or sensitisation effects. Also, the pH of such compounds, consisting of the neutralisation product of a weak base (bismuth hydroxide) and a weak acid (naphthenic acids) is expected being neutral, and experience in production and use does confirm this. Even the slight excess of naphthenic acids, used in production to shift the reaction towards tri-substitution, does not change the pH significantly. As a result, it is assumed that the skin barrier remains intact upon exposure.
However, it is expected that the slight excess of naphthenic acids, used to shift the reaction towards tri-substitution, will mainly determine the skin sensitisation potential of the UVCB substance, and naphthenic acids, due to a much smaller molecular size will be potentially capable of passing human skin. Thus, the focus for assessing skin sensitisation will be on naphthenic acids. Bismuth hydroxide nitrate oxide at concentrations of 10%, 25% or 50% (w/w) in acetone/olive oil (3+1, v/v) did not reveal any sensitising properties in the local lymph node assay, and therefore even soluble bismuth(III) compounds are not leading to skin sensitisation.
The source substance naphthenic acids has been investigated for skin sensitisation properties in an in vivo OECD 406 Guinea pig maximisation test (Yamato et al., 2006). The results did indicate that naphthenic acids were positive in the guinea pig maximisation test.
Thus, it can be concluded, that although the bismuth(III) cation will not cause skin sensitisation, the naphthenic acids are considered skin sensitising. Taking into account that naphthenic acids, bismuth salts are manufactured with a slight excess of naphthenic acids (to ensure tri-substitution), excess naphthenic acids will be present in the UVCB substance and thus the target substance naphthenic acids, bismuth salts is considered being a skin sensitiser.

4. DATA MATRIX
The source substances naphthenic acids and bismuth hydroxy nitrate oxide were assessed in studies to investigate skin sensitisation properties; the bismuth compound in an in vivo local lymph node assay and the naphthenic acids in an in vivo guinea pig maximisation test (OECD 406). Whereas the soluble bismuth 3+ form was found negative for skin sensitisation, the naphthenic acids showed clearly skin sensitising effects.
Considering that the target substance consists of approx. 90% bismuth tri-naphthenates and a slight excess of free naphthenic acids (~10%) it is clear that the skin sensitising effect of naphthenic acids is relevant for classification and labelling as well as risk assessment of the target substance naphthenic acids, bismuth salts, being considered as a skin sensitiser, accordingly.
In conclusion, the naphthenic acids, bismuth salts are considered as skin sensitiser, category 1 according to CLP (Regulation EC No 1272/2008).

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

5

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

4

Total no. in group:

5

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Remarks on result:

other: not reported in publication, but due to positive results not considered critical.

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Based on data from naphthenic acids, that target substance naphthenic acids, bismuth salts is considered being a skin sensitiser.

Executive summary:

The source substance naphthenic acids has been investigated for skin sensitisation properties in an in vivo OECD 406 Guinea pig maximisation test (Yamato et al., 2006). The results did indicate that naphthenic acids were positive in the guinea pig maximisation test.

Thus, it can be concluded, that although the bismuth(III) cation will not cause skin sensitisation, the naphthenic acids are considered skin sensitising. Taking into account that naphthenic acids, bismuth salts are manufactured with a slight excess of naphthenic acids (to ensure tri-substitution), excess naphthenic acids will be present in the UVCB substance and thus the target substance naphthenic acids, bismuth salts is considered being a skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on skin sensitising properties attributable to naphthenic acids, the substance naphthenic acids, bismuth salts is classifed as skin sensitising, category 1 according to CLP (Regulation EC No. 1272/2008).