Registration Dossier

Administrative data

Description of key information

Diantimony trioxide elicits skin irritation potential only under conditions of high chemical dermal exposure and severe sweating.

Diantimony trioxide is not eye irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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):

Skin:

The Committee for Risk Assessment (RAC) of the European Chemicals Agency (ECHA) concluded that a harmonised classification of irritating to skin was not supported, since special conditions, namely substantial heat and sweat, were required in addition to high chemical dermal exposure in all the cases where skin effects had been described in the workplace (ECHA/PR/09/09, Helsinki, 06 July 2009). Furthermore, it was unclear whether diantimony trioxide was the only chemical substance to which these workers had been exposed in some studies.

Eye:

In a recent (Leuschner, 2005) very well-conducted and reported acute eye irritation/corrosion test with highly pure diantimony trioxide, performed according to OECD guideline 405 and in compliance with GLP regulations, the only observation was conjunctival redness (grade 1) observed in 2 animals at 24 and 24 to 72 hours after installation, respectively. There were no corneal lesions, the iris was not affected by instillation of the item, and there were no systemic intolerance reactions.

In contrast, in a rather dated study (1979) conducted in the early stages of GLP implementation and prior to the establishment of OECD test guidelines, “antimony oxide” (without further specification) of unknown purity and composition was tested. The designated source (“PPG Industries”) is a company that nowadays fabricates coatings; it may therefore be speculated that the powder that was tested may not have been only an “antimony oxide” of sorts, but perhaps a flame retardant or other preparation. Given the poor hygiene of eye irritant testing facilities at the time and in particular a lack of “specific pathogen free” conditions, it may be questioned whether the good health in which the animals were claimed to be could really be established beyond doubt. Because of the poorly defined test substance and the questionable health status of the test animals in this study, it was concluded in a weight-of-evidence approach to assign higher reliability to the more recent GLP- and guideline-conform study.

Respiratory tract

In an acute inhalation study with antimony trioxide in rats (Leuschner, 2006), in which irritation of the respiratory tract was also evaluated, no signs of respiratory tract irritation were found. In five case report studies on workers occupationally exposed to antimony trioxide, effects that could indicate irritation in the respiratory tract have been described. However, there is very little information concerning exposure in these studies and it is unclear whether antimony trioxide was the causative agent. Based on the available data antimony trioxide (and by read-across also diantimony tris(ethylene glycolate)) can be concluded not to be irritating to the respiratory system.

Justification for selection of skin irritation / corrosion endpoint:

Key study

Justification for selection of eye irritation endpoint:

Key study

Justification for classification or non-classification

Skin irritation:

The Committee for Risk Assessment (RAC) of the European Chemicals Agency (ECHA) concluded that a harmonised classification of irritating to skin was not supported, since special conditions, namely, substantial heat and sweat, were required in addition to high chemical dermal exposure, in all the cases where skin effects had been described in the workplace (ECHA/PR/09/09, Helsinki, 06 July 2009). Furthermore, it was unclear whether diantimony trioxide was the only chemical substance to which these workers had been exposed in some studies.

Eye irritation:

Reference Leuschner (2005) is considered as the key study for eye irritation and will be used for classification. The overall irritation results are as follows:

The classification criteria according to regulation (EC) 1272/2008 as irritating to eyes are not met since the mean score for corneal opacity, iritis, conjunctival oedema after 24, 48 and 72 h was each time 0.0 and the mean score for conjunctival redness was 0.44, hence no classification required. The classification criteria according to regulation (EC) 1272/2008 as irritating to eyes are not met since the mean score after 24 h was 0.4, hence no classification required.

Respiratory irritation:

The justification for non classification as respiratory irritant is covered under the endpoint specific target organ toxicity- single exposure as given in the acute toxicity section.

 

No data available that concluded respiratory irritation is present after repeated inhalation exposure. However, due to the fact that an acute inhalation toxicity test at the an exposure of 5.2mg/L revealed no relevant pulmonary changes in the 5 localisations of the lung, neither in the rats sacrificed at 24 hours after exposure nor of rats sacrificed 14 days after exposure, one may safely conclude that diantimony trioxide (and by read-across also diantimony tris(ethylene glycolate)) is void of any irritating potential towards the respiratory tract.