Registration Dossier

Administrative data

Description of key information

Based on the fact that diantimony pentoxide, sodium hexahydroxoantimonate and sodium antimonate contain antimony in the pentavalent oxidation state and that water solubility testing as well as transformation dissolution testing has shown similar dissolution pattern of pentavalent antimony cations form all three substances, read-across among the pentavalent antimony compounds (i.e. sodium hexahydroxoantimonate, sodium antimonate and diantimony pentoxide) is considered justified.

 

No test item related changes were observed in a 90-day repeated dose toxicity study via oral route up to the limit dose of 1000 mg/kg bw/day with sodium hexahydroxoantimonate. The no-observed-effect level (NOEL) was above 1000 mg sodium hexahydroxoantimonate/kg b.w./day, p.o. for the male and female rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
One key study available (90-day repeated dose toxicity study in rats according to OECD 408, under GLP) which is reliable without restrictions (RL=1). The overall quality of the database is therefore high.

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

Three oral dose levels of sodium hexahydroxoantimonate were evaluated in a 90-day repeated dose toxicity study in rats. Four groups of 10 male and female animals were treated orally via gavage with dose levels of 0, 100, 300 and 1000 mg/kg bw/d in Methocel once daily. In addition, 5 male and 5 female animals in the high and control group were held as recovery. Animals in the main group were sacrificed on test day 91, animals in the recovery group were sacrificed on test day 119.

None of the rats died prematurely and no test item-related influence was noted on the behaviour or external appearance of the male and female rats. The observational screening, the examination of the fore- and hindlimb grip strength as well as the spontaneous motility did not reveal any test item-related changes. The body weight, body weight gain, food and drinking water consumption, the haematological, biochemical and urinary parameters examined were in the normal range of variation. No test item-related changes were observed at ophthalmological examination. No treatment-related influence was noted on the number of ultrasound resistant spermatids, the number of motile spermatozoa and the sperm morphology of the male rats.

The necropsy as well as the histopathological examination of the organs examined did not reveal any macroscopic or microscopic lesions. The relative and absolute organ weights were in the normal range of variation.

 

Under the present test conditions the no-observed-effect level (NOEL) was above 1000 mg Sodium hexahydroxoantimonate/kg b.w./day, p.o. for the male and female rats.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

Key study

Justification for classification or non-classification

Based on the fact that diantimony pentoxide, sodium hexahydroxoantimonate and sodium antimonate contain antimony in the pentavalent oxidation state and that water solubility testing as well as transformation dissolution testing has shown similar dissolution pattern of pentavalent antimony cations form all three substances, read-across among the pentavalent antimony compounds (i.e. sodium hexahydroxoantimonate, sodium antimonate and diantimony pentoxide) is considered justified.

The reference Hansen (2013) is considered as the key study for repeated dose toxicity via oral application and will be used for classification. Rats were dosed at 0, 100, 300 and 1000 mg/kg bw/day orally via gavage. Based on the lack of any adverse effects, the no observed effect level (NOEL) via oral application for sodium hexahydroxoantimonate was established at > 1000 mg/kg bw/day.

 

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – repeated exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and the no observed effect level (NOEL) via oral application is above the guidance value for a Category 1 classification of 10 mg/kg bw/day and above the guidance value for a Category 2 classification of 100 mg/kg bw/day. For the reasons presented above, no classification for specific target organ toxicant (STOT) – repeated exposure, oral is required for pentavalent antimony compounds such as sodium hexahydroxoantimonate, sodium antimonate and antimony pentoxide.