Bismuth tris(2-ethylhexanoate)

Endpoint summary

Description of key information

No acute toxicity studies with bismuth tris (2-ethylhexanoate) are available, thus the acute toxicity will be addressed with existing data on the dissociation products bismuth and 2-ethylhexanoate.

Signs of acute oral or acute dermal toxicity are not expected for bismuth tris (2 -ethylhexanoate). The two assessment entities bismuth and 2-ethylhexanoic acid have not shown signs of acute oral toxicity in experimental testing (both LD50 > 2000mg/kg). The assessment entity 2 -ethylhexanoic acid has not shown signs of acute dermal toxicity in experimental testing. The assessment entity bismuth is assumed not to show any signs of acute toxicity upon dermal exposure, due to its very poor percutaneous absorption.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Bismuth

 

Acute toxicity: oral

In an acute oral toxicity test in rats with bismuth (mean particle diameter was 10 µm), no deaths occurred at a dose of 2000 mg/kg body weight. Therefore the LD50 is >2000 mg/kg bw for both sexes.

 

Acute toxicity: dermal

In the absence of measured data on dermal absorption, current guidance suggests the assignment of either 10 % or 100 % default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of metals yields substantially lower figures, which can be summarised briefly as follows:

Measured dermal absorption values for metals or metal compounds in studies corresponding to the most recent OECD test guidelines are typically 1 % or even less. Therefore, the use of a 10 % default absorption factor is not scientifically supported for metals. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn) and current metal risk assessments under REACH, which have derived dermal absorption rates of 2 % or far less (but with considerable methodical deviations from existing OECD methods) from liquid media.

However, considering that under industrial circumstances many applications involve handling of dry powders, substances and materials, and since dissolution is a key prerequisite for any percutaneous absorption, a factor 10 lower default absorption factor may be assigned to such “dry” scenarios where handling of the product does not entail use of aqueous or other liquid media. This approach was taken in the in the EU RA on zinc. A reasoning for this is described in detail elsewhere (Cherrie and Robertson, 1995), based on the argument that dermal uptake is dependent on the concentration of the material on the skin surface rather than it’s mass.

The following default dermal absorption factors for metal cations are therefore proposed (reflective of full-shift exposure, i.e. 8 hours):

From exposure to liquid/wet media: 1.0 %

From dry (dust) exposure: 0.1 %

This approach is consistent with the methodology proposed in HERAG guidance for metals (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal compounds; EBRC Consulting GmbH / Hannover /Germany; August 2007).

2-ethylhexanoate

 

Acute oral toxicity

In an acute oral toxicity study 4 rats/sex/dose were dosed with 90, 722, 1445 or 2890 mg/kg bw. No mortality was observed in the 90, 722 and 1445 mg/kg bw dose groups. The test material caused mortality in rats administered a dose of 2890 mg/kg bw (4/4), and transitory weakness at lower doses in a dose-dependent manner. The LD50 was calculated to 2043 mg/kg bw.

 

In another acute oral toxicity study 5 rats/sex/dose have been administered 0.2, 1.6, 3.2 and 4.0 ml 2-ethylhexanoic acid/ kg bw. No substance related clinical signs nor mortality was observed at 0.2 and 1.6 ml/kg. However, 1/10 animals died. After administration of 3.2 ml/kg and 4 ml/kg apathy dyspnea abdominal position and re crusted eyes and snouts were observed. Mortality in these dose groups was 3/10, 5/10, respectively. LD 50 was estimated to be 4 mL/kg bw, being equivalent to 3640 mg/kg bw (density 0.91 g/ml). This result is supported by another study which however was poorly documented.e no signs of a toxicity response.  It is concluded that the LD50 is greater than 3640 mg/kg. This result is supported by another study which however was poorly documented.

 

Acute dermal toxicity

Dermal toxicity of 2-ethylhexanoic acid was tested in an OECD 402 guideline study. Five Wistar rats/sex/dose have been exposed dermally (semi-occlusive to a limit dose of 2000 mg/kg bw 2‑ethylhexanoic acid. No mortality and no clinical symptoms beside eschar formation have been observed.LD50 dermal therefore is > 2000 mg/kg bw.

Bismuth tris (2-ethylhexanoate)

Signs of acute oral or acute dermal toxicity are not expected for bismuth tris (2 -ethylhexanoate). The two assessment entities bismuth and 2-ethylhexanoic acid have not shown signs of acute oral toxicity in experimental testing (both LD50 > 2000mg/kg). The assessment entity 2 -ethylhexanoic acid has not shown signs of acute dermal toxicity in experimental testing. The assessment entity bismuth is assumed not to show any signs of acute toxicity upon dermal exposure, due to its very poor percutaneous absorption.

Under the assumption that the moieties of bismuth tris (2-ethylhexanoate) show their toxicological profile individually upon dissolution, the acute oral and dermal (systemic) toxicity of bismuth tris (2-ethylhexanoate) can be calculated using the equation given in regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1.

A study for acute toxicity via inhalation was not conducted with bismuth tris (2-ethylhexanoate), since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

 

The calculated oral and dermal LD50 for bismuth tris (2-ethylhexanoate) is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

Justification for classification or non-classification

Based on in vivo oral and dermal LD50 data on the moieties, acute toxicity estimates for bismuth tris (2-ethylhexanoate) have been calculated resulting in LD50 values > 2000 mg/kg bw.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, bismuth tris (2-ethylhexanoate) does neither have to be classified and has no obligatory labelling requirement for acute oral or dermal toxicity nor for specific target organ toxicity after single exposure (STOT SE).