Registration Dossier

Administrative data

Description of key information

Oral:

 

Two repeated dose oral studies (Sunagawa, 1981; Hext et al., 1999) suggest that diantimony trioxide may be toxic to the liver. This being based on a 10 % increase in liver weight. In addition, one study (Hext et al., 1999) exhibited significantly elevated ASAT values and significantly decreased ALP values. The other study (Sunagawa, 1981) revealed both ASAT and ALP levels to be significantly elevated. However, in the absence of histological change or any clinical signs of antimony intoxication to support liver adversity, the differences are regarded as adaptive or incidental to treatment with diantimony trioxide. A NOAEL of 1686 mg/kg/d for liver toxicity is suggested.

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
1 686 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 407, under GLP) which is reliable with minor restrictions (RL=2). The overall quality of the database is therefore high.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The is no indication for systemic toxicity in several repeated dose toxicity studies via oral and inhalation route, thus a NOAEC for inhalation, systemic toxicity is not identified.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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

Justification for classification or non-classification

Repeated dose toxicity, oral:  

The reference Hext P. M., Pinot P. J. and Rimmel B. A. (1999) is considered as the key study for repeated dose toxicity via oral application and will be used for classification. Rats were dosed at 20,000 ppm/day orally via feed for 90 days. Based on the lack of any adverse effects, the no observed adverse effect level (NOAEL) via oral application for diantimony trioxide was established at 1686 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 adverse effect level (NOAEL) 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.

Repeated dose toxicity, dermal:   No classification for specific target organ toxicant (STOT) – repeated exposure, dermal is required.

Repeated dose toxicity, inhalation: No classification for specific target organ toxicity (STOT) - repeated exposure, inhalation is required