Registration Dossier

Administrative data

Description of key information

The acute toxicity of arsenic compounds has been studied to great extent in animal studies and there are also many case reports of acute effects in humans. The focus of such investigations has been on oral exposure. LD50s (oral) reported for diarsenic trioxide in peer-reviewed factual databases are in the range from ca. 10-214 mg/kg, which is in agreement with the existing harmonized classification as "Acute Tox 2" according to Regulation (EC) No 1272/2008. Available data do not justify a classification for acute inhalation or dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Additional information

The acute toxicity of arsenic compounds has been studied to great extent in animal studies and there are also many case reports of acute effects in humans. The focus of such investigations has been on oral exposure. Because of the enormous amount of data, reference is made to available reviews, such as the "Toxicological Profile for Arsenic (ATSDR, 2007), or to peer-reviewed factual databases, such as the Hazardous Substance Databank (HSDB) and the Registry of Toxic Effects of Chemical Substances (RTECS).

For diarsenic trioxide, reported oral LD50s in animals are in the range from ca. 10-214 mg/kg, which is in agreement with the existing harmonized classification as "Acute Tox 2" according to Regulation (EC) No 1272/2008. Human case reports of accidental or deliberate poisoning support the conclusion that diarsenic trioxide is acutely toxic via the oral route.

Acute inhalation exposure of humans to diarsenic trioxide usually does not take place to a significant extent and does not usually lead to death, but irritation of skin and mucous membranes have been observed (in agreement with the existing harmonised classification as Skin Corr. 1B). After evaluation of all available data (existing reviews, literature searches in factual and bibliographic databases) a reliable standard toxicity descriptor value, such as a LC50(4h), cannot be established for diarsenic trioxide. A standard acute inhalation toxicity study (e.g. OECD 403 or comparable guideline) is not available. Some animal studies are available which used intratracheal injection as the route of exposure, but are not focused on lethality as an endpoint, but rather on local lung effects, lung clearance issues or carcinogenicity.

Adverse effects from dermal exposure to inorganic or organic arsenicals have not been extensively investigated. No studies were located regarding death in humans after dermal exposure to inorganic arsenicals. In rats, no deaths resulted from dermal exposure to arsenate or arsenite at doses up to 1,000 mg As/kg. These data indicate that dermal exposure to inorganic arsenic compounds is very unlikely to result in death. According to reliable reviews, the dermal absorption of inorganic arsenic compounds is considered to be low (<10%), rendering this route of exposure to be of limited relevance.

Due to the well known toxicological profile of arsenic compounds, including diarsenic trioxide, and specifically because of the carcinogenic potential, strict measures are already in place to exclude or minimise as far as possible any exposure of humans to such compounds. Therefore, and for animal welfare reasons, it is not justified to conduct further toxicological studies in experimental animals.

Justification for classification or non-classification

Diarsenic trioxide is classified as "Acute Tox 2" according to Regulation (EC) No 1272/2008 based on a large database of human and animal data. LD50s (oral) reported for diarsenic trioxide in peer-reviewed factual databases are in the range from ca. 10-214 mg/kg. Available data do not justify a classification for acute inhalation or dermal toxicity for diarsenic trioxide.