Bismuth tris(2-ethylhexanoate)

Endpoint summary

Description of key information

No repeated dose toxicity study with bismuth tris (2-ethylhexanoate) is available, thus the repeated dose toxicity will be addressed with existing data on the individual assessment entities bismuth and 2-ethylhexanoate.

In relevant and reliable repeated dose toxicity studies for both assessment entities of bismuth tris (2-ethylhexanoate), there were no toxicological findings reported that would justify a classification for specific target organ toxicity with repeated exposure.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Bismuth

In an available publication, bismuth ions show no significant changes attributed to treatment with bismuth on clinical signs, body weights, food consumption, haematology, clinical chemistry, urinalysis, organ weights, necropsy, or histopathological findings in a 28-day repeated oral dose toxicity study. As a result of the findings, the NOAEL was determined to be 1000 mg/kg for males and females.

 

The oral (gavage) administration of Bismuth Subnitrate to male and female Wistar Han™:RccHan™:WIST strain rats for 90 days at dose levels up to 1000 mg/kg bw/day was well tolerated.

There was no adverse effect of treatment on body weight development and dietary intake in animals of either sex. Hematology, blood chemistry, testosterone hormone assessment, estrus cycle assessment in females, sperm analysis in males and microscopic examination of the selected tissues did not identify any findings of toxicological relevance. A dose level of 1000 mg/kg bw/day is therefore considered to be the ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity within the confines of this type of study.

 

2-ethylhexanoic acid

Several repeated oral dose studies for 2-ethylhexanoic acid were available for assessment. A diet containing 0.5% 2-ethylhexanoic acid caused no adverse effect in rats in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%, calculated NOAEL ca. 300 mg/kg bw/day). No adverse effect was observed in mice receiving a diet containing 0.5 % 2-ethylhexanoic acid in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%). The NOAEL was calculated to be 200 mg/kg bw/day. Both NOAELs were based on reduced food consumption and a decreased rate of body weight gain in the high dose groups. In both studies, all toxicity observed at higher concentrations (changes in clinical chemistry, absolute and relative organ weights, microscopic changes in kidney liver and fore stomach) was reversible within 28 days after exposure ceased.

Based on the absence of any (severe) adverse effects at low doses in subacute and semichronic toxicity study with a.o. rats, classification for repeated dose toxicity is not warranted according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

Bismuth tris (2-ethylhexanoate)

Since no repeated dose toxicity study is available specifically for bismuth tris (2-ethylhexanoate), information on the individual assessment entities bismuth and 2-ethylhexanoate will be used for the hazard assessment and when applicable for the risk characterisation of bismuth tris (2-ethylhexanoate). For the purpose of hazard assessment of bismuth tris (2-ethylhexanoate), the point of departure for the most sensitive endpoint of each assessment entitiy will be used for the DNEL derivation. In case of 2-ethylhexanoic acid in bismuth tris (2-ethylhexanoate), the NOAEL of 100 mg/kg bw/day for the developmental toxicity will be used. In case of bismuth the NOAEL of 714.7 mg Bi/kg bw/day obtained in a repeated dose toxicity study will be used.

Justification for classification or non-classification

In relevant and reliable repeated dose toxicity studies for both moieties of bismuth tris (2-ethylhexanoate), there were no toxicological findings reported that would justify a classification for specific target organ toxicity - repeated exposure. Hence, no classification for bismuth tris (2-ethylhexanoate) as STOT- RE (oral) is required.