Naphthenic acids, bismuth salts

Endpoint summary

Description of key information

Skin

The source substances naphthenic acids and bismuth hydroxide were assessed in studies to investigate skin corrosion/irritation; the bismuth compound in an in vitro reconstructed human epidermis study and the naphthenic acids in an in vivo study (combined OECD 402/404 study) and both source substances were found negative for skin corrosion and skin irritation. The naphthenic acids showed slight sign of skin irritation, but well below the threshold for classification according to CLP (Regulation EC No 1272/2008).

Considering that the target substance consists of approx. 90% bismuth tri-naphthenates and a slight excess of free naphthenic acids (~10%), it is assumed that the slight skin irritation potential of naphthenic acids is even weaker in the target compound and therefore, it can be reasonably assumed that the target compound is not to be considered corrosive or irritant to skin.

Considering the high molecular weight of the main target compound (~ 850 Dalton for the bismuth tri-naphthenates) which makes passing the skin barrier extremely unlikely, supported by the in vitro results on bismuth hydroxide showing no potential for skin irritation, the in vivo results on naphthenic acids will be decisive for assessing skin corrosion/irritation potential. In conclusion, no potential for skin corrosion/irritation of the target substance is derived.

Eyes

The source substances naphthenic acids and bismuth hydroxide were assessed in in vivo studies to investigate eye damage/irritation; whereas the source substance bismuth hydroxide in an in vivo study (OECD 405 study) was found negative for eye damage/irritation, the source substance naphthenic acids in an in vivo study (OECD 405 study) showed a moderate eye irritation reaction, which was found being fully reversible.

Considering that the target substance consists of approx. 90% bismuth tri-naphthenates and a slight excess of free naphthenic acids (~10%) it is assumed that the moderate eye irritation potential of naphthenic acids is weaker in the target compound. Nevertheless, in a worst-case approach, it can be conservatively assumed that the target compound is to be considered an irritant to eyes.

In conclusion, the target compound naphthenic acids, bismuth salts is considered irritant to eyes, classified according to CLP to category 2 for eye irritation.

Respiratory tract

Data on respiratory irritation are not available, but so far no reportings by workers were made and considering the very low vapour pressure (<1 Pa) and non-aerosol use (the substance is an additive to industrial heavy duty grease), respiratory exposure is very unlikely.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Remarks:

decisive, but supported by read across to in vitro study on Bi(OH)3

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 corrosivity and skin irritation, 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 corrosivity/irritation 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.

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 corrosion or irritation 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 corrosion/irritation 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 acute skin corrosion/irritation potential will be on naphthenic acids. Bismuth hydroxide, having been assessed in a reconstructed human epidermis test (in vitro EPISKIN), has shown not to be corrosive or irritant to skin.
The source substance naphthenic acids has been investigated for skin irritation in an in vivo OECD 404 like study (Exxon 1979) with dermal application to rabbit skin. A dose of 3.16 g/kg bw was applied and no mortality was observed. Following exposure for 24 hours mean values (24, 48 & 72 hours) for erythema and edema at the intact sites were 1.69/4 and 1.3/4, respectively. All symptoms were reversible during 14 days observation period.
Thus, it can be concluded, that both, the bismuth(III) cation as well as the naphthenic acids have a low potential for irritation of human skin, especially when considering the very low water solubility of the target substance that was determined being < 0.036 mg/L and the expected low absorption rate.

4. DATA MATRIX
The source substances naphthenic acids and bismuth hydroxide were assessed in studies to investigate skin corrosion/irritation; the bismuth compound in an in vitro reconstructed human epidermis study and the naphthenic acids in an in vivo study (combined OECD 402/404 study) and both source substances were found negative for skin corrosion and skin irritation. The naphthenic acids showed slight sign of skin irritation, but well below the threshold for classification according to CLP (Regulation EC No 1272/2008).
Considering that the target substance consists of approx. 90% bismuth tri-naphthenates and a slight excess of free naphthenic acids (~10%) it is assumed that the slight skin irritation potential of naphthenic acids is even weaker in the target compound and therefore, it can be reasonably assumed that the target compound is not to be considered corrosive or irritant to skin.
Considering the high molecular weight of the main target compound (~ 850 Dalton for the bismuth tri-naphthenates) which makes passing the skin barrier extremely unlikely, supported by the in vitro results on bismuth hydroxide showing no potential for skin irritation, the in vivo results on naphthenic acids will be decisive for assessing skin corrosion/irritation potential.
No potential for skin corrosion/irritation of the target substance is derived.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 4 animals

Time point:

24/48/72 h

Score:

1.69

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 4 animals

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

It is expected that the slight excess of naphthenic acids, used to shift the reaction towards tri-substitution, will mainly determine the skin corrosion/irritation potential of the UVCB substance and the results for pure naphthenic acids have been reported here. Naphthenic acids, due to a much smaller molecular size compared to bismuth tri-naphthenate will be potentially capable of passing human skin. Thus, the focus for assessing acute skin corrosion/irritation potential will be on naphthenic acids. Bismuth hydroxide, having been assessed in a reconstructed human epidermis test (in vitro EPISKIN), has shown not to be corrosive or irritant to skin.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on negative results from an in vitro skin irritation study with bismuth hydroxide and only slight skin irritation effects seen in an in vivo skin irritation study with naphthenic acids, it can be concluded that the target compound naphthenic acids, bismuth salts is non-irritant to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Whereas based on study results the substance naphthenic acids, bismuth salts is considered non-irritant to skin, an irritation of eyes cannot be excluded, due to the residual naphthenic acids being a minor component in the target substance. Data on respiratory irritation are not available, but so far no reportings by workers were made and considering the very low vapour pressure (<1 Pa) and non-aerosol use (the substance is an additive to industrial heavy duty grease), respiratory exposure is very unlikely. In conclusion, the substance is conservatively classified as eye irritant, category 2, according to CLP (Regulation EC No. 1272/2008).