Registration Dossier

Administrative data

Description of key information

LD50 (oral ): >20000mg/kg bw/day

LD50 (dermal): >8300mg/kg bw

LC50 (inhalation): >5200mg/m³

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Five weight of evidence studies available which are old and do not comply with today standards. However, a conclusive statement about the LD is possible using that data, thus the overall quality of the database is therefore sufficient.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
One key study available (according to OECD 403, under GLP) which is reliable without restrictions (RL=1). The overall quality of the database is therefore high.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
One key study available which is reliable with minor restrictions (RL=2). The overall quality of the database is therefore high.

Additional information

Upon dissolution in aqueous media at physiologically relevant concentrations and pH conditions, the only aqueous antimony species emerging from all considered trivalent antimony substances is the trivalent antimony cation. In vitro bioaccessibility testing in various artificial body fluids (Hedberg et al., 2010) has shown that diantimony tris(ethylene glycolate) compared to diantimony trioxide has a lower release rate of antimony ions, thus read-across warrants an intrinsic conservatism.

With respect to systemic toxicity, read-across from diantimony trioxide toward diantimony tris(ethylene glycolate) is justified. 

Please also refer to the study results presented in section 4.8 and 7.1.1 of the technical dossier (IUCLID) and in section 1.3 and 5.1.1 of the CSR.

The following conclusions can be drawn for diantimony trioxide and by read across, also for diantimony tris(ethylene glycolate):

For acute inhalation toxicity there is one animal study (Leuschner, 2006) which has been performed according to OECD TG 403 and which shows no signs of acute toxicity after inhalation exposure to diantimony trioxide, indicating a LC50 > 5.20 mg/ L (5200 mg/ m³). The animal studies on acute oral exposure are all old (Fleming, 1938; Gross et al., 1955; Myers et al., 1978), they do not comply with today standards and in most of them mortality was the only parameter investigated as they were designed to determine at what dose level death occurred. Still, they indicate that oral LD50 is in excess of 20000 mg/kg bw in rats. There is one valid study on dermal exposure (Gross et al., 1955), which indicates that the LD50 for dermal exposure is higher than 8300 mg/kg bw. In conclusion, diantimony trioxide is of low acute inhalation, oral and dermal toxicity.

Justification for selection of acute toxicity – oral endpoint

Weight of evidence information

Justification for selection of acute toxicity – inhalation endpoint

Key study

Justification for selection of acute toxicity – dermal endpoint

Key study

Justification for classification or non-classification

Acute oral toxicity

The animal studies on acute oral exposure are all old, they do not comply with today standards and in most of them mortality was the only parameter investigated as they were designed to determine at what dose level death occurred. Still, they indicate that oral LD50 is in excess of 20,000 mg/kg bw in rats which will be used for classification purposes.

LD50 oral, rat > 20,000 mg/kg bw

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2,000 mg/kg body-weight, hence no classification required.

 

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw. No classification required.

 

Acute inhalation toxicity

The reference Leuschner (2006) is considered as the key study for acute inhalation toxicity and will be used for classification. Rats were nose only exposed towards diantimony trioxide dust for 4 hours at 5.2 mg/L air. During the conduct of the study no mortalities occurred.

LC50 inhalation, rat > 5.2 mg/L air

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE for dusts and mists is above 5.0 mg/L, hence no classification required.

 

Specific target organ toxicant (STOT) – single exposure: inhalation

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation dust/mist/fume are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance values, inhalation dust/mist/fume for a Category 1 classification of 1.0 mg/L/4 h and at the guidance value or inhalation dust/mist/fume for a Category 2 classification of 5.0 mg/L/4 h. Therefore, no classification is required. However, such classification is also not warranted, since observations on respiratory irritation in test animals were not observed at the highest inhalation exposure level. No relevant pulmonary changes were observed in the 5 localisations of the lung neither in the rats sacrificed 24 hours after exposure nor the rats sacrificed 14 days after exposure.