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Description of key information

Repeated dose toxicity via the oral route:  NOAEL of bismuth was determined to be 1000 mg/kg for male and female rats in a subacute toxicity study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Repeated oral toxicity:

According to Annexes VIII and IX, point 8.6 of Regulation No 1907/2006 information on repeated dose toxicity of substances shall be provided.

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.

In addition to fulfil the data requirements for a substance imported or manufactured in quantities >1000 t/y according to the Annex IX of the regulation (EC) 1907/2006, a 90-day oral toxicity study in rats according to OECD guideline 408 is proposed.

Repeated dermal toxicity:

A dermal repeated dose toxicity study for bismuth metal is considered to be scientifically unjustified.

Repeated inhalation toxicity:

No reliable or relevant studies or data are available for bismuth metal. One publication about intratracheal administration of bismuth to rats for 13 weeks is available. But the exposure route is not reliable for risk assessment. However, results showed that dose-dependent, but not specific adverse effects, were attributable to bismuth administration in the rat.

Due to a lack of route-specific toxicity data, the health risk will be assessed by route to route extrapolation based on the subchronic oral study with bismuth hydroxide nitrate oxide (see above). Read across between bismuth hydroxide nitrate oxide and bismuth metal is considered feasible without restriction with the following rationale: Bismuth substances dissociate in water to Bi3+and the anionic counter-ions and it can be assumed that potential effects are caused by Bi3+. In addition, bismuth is absorbed rapidly after oral dosing evident by an increased bismuth concentration in blood, even though the absorption rate is very low. Most of the ingested bismuth (ions) is excreted via faeces.

The results from the subchronic oral toxicity study will be chosen as the most suitable starting point for the route to route extrapolation. The obtained NOAEL will be, among other, corrected for the substance (read across), respiratory volume (the default respiratory volume value for the rat corresponding to 6 hour daily exposure is used (see Table R.8-2 in ECHA guidance) and inhalation absorption factor.

Justification for classification or non-classification

Repeated oral toxicity:

Guideline compliant repeated dose toxicity studies in rodents with oral administration of bismuth metal (28-day study according to OECD 407 or 90-day study according to OECD 408) are not available. The only available reference for bismuth (28-day exposure) allow a derivation of a NOAEL of 1000 mg/kg bw.

In addition to fulfil the data requirements for a substance imported or manufactured in quantities >1000 t/y according to the Annex IX of the regulation (EC) 1907/2006, a 90-day oral toxicity study in rats according to OECD guideline 408 is proposed.

Since no all data are available to fulfil the data requirement for a substance imported or manufactured in quantities >1000 t/y according to the regulation (EC) 1907/2006, classification concerning repeated oral toxicity cannot be done yet.

Repeated inhalation toxicity:

No reliable or relevant studies or data are available for bismuth metal. Due to a lack of route-specific toxicity data, the health risk will be assessed by route to route extrapolation based on the proposed subchronic oral study with bismuth hydroxide nitrate oxide (see above). Read across between bismuth hydroxide nitrate oxide and bismuth metal is considered feasible without restriction.

Since no relevant data are available for bismuth metal, classification concerning repeated inhalation toxicity cannot be done yet.

Repeated dermal toxicity:

Dermal repeated dose toxicity is considered to be scientifically unjustified. No data are available; classification concerning repeated dermal toxicity is not required.