Arsenic trioxide

trioxide]]
**Arsenic trioxide**, also known as **white arsenic**, **arsenic(III) oxide**, or **arsenious oxide**, is a chemical compound. Its chemical formula is As2O3. It has arsenic and oxide ions in it. The arsenic is in its +3 oxidation state. It is very toxic. At very low dose it can be used to treat acute promyelocytic leukemia (APL), a type of blood cancer.

## Properties
Arsenic trioxide is a white solid. It dissolves in water to make an acidic solution of arsenious acid. It dissolves easily in bases to make arsenites. It reacts with concentrated hydrochloric acid to make arsenic trichloride. It reacts with very strong oxidizing agents to make arsenic pentoxide. It reacts with reducing agents to make arsenic or arsine. It sublimes much easier than metal oxides, making it easy to separate by heating the mixture.

## Occurrence and preparation
Arsenic trioxide is rarely found as a mineral. It is normally made from orpiment or realgar, arsenic sulfide minerals. About 50,000 tons of arsenic trioxide are made each year. Arsenic trioxide is made by burning arsenic in air, reacting arsenic with concentrated sulfuric acid, or the roasting of arsenic sulfide ores.

## Safety
Arsenic trioxide is highly toxic when eaten. It also can be toxic if on the skin for long amounts of time. It affects the digestive system when eaten. Workers exposed to arsenic trioxide fumes in their job can be poisoned as well.

## Uses
It is used to make elemental arsenic. It was used as a pigment (in Paris green) and as a wood preservative but was banned in many countries because it is so toxic.

### Medical 
#### Treatment of Acute promyelocytic leukemia 
Arsenic trioxide is used to fight acute promyelocytic leukemia (APL).

Various forms of arsenic were used in China for over 2000 years. Arsenic first appeared in Western Medicine in the eighteenth century. In hematology, oral arsenic was first reported in the treatment of chronic myeloid leukemia from the 1860s to 1920s in Germany and Boston City. This treatment was phased out following World War II with the development of alkylating chemotherapy and radiotherapy. Intravenous pure As2O3 solution was first used in Harbin, China in 1973

In March 1971, Han Taiyun of the 1st Affiliated Hospital started to treat cancer patients with a formula he collected from traditional Chinese medicine doctors. It was presumably an oral formula, and contained a mixture of many ingredients, including arsenic chemicals, mercury chloride, and cinobufagin venom toad. Later, Han Taiyun turned the formula into an intramuscular injection called "713" or "cancer spirit". For certain tumors, it worked and became a local hit. But Han Taiyun gave that treatment up because the formula was too toxic for some patients.

Zhang Tingdong is a doctor of Traditional Chinese Medicine at First Clinical Hospital, affiliated with Harbin Medical University in Harbin, a city in the far north of China. He is also a hematologist (blood specialist).

In 1972, Zhang started to cooperate with Han Taiyun. Instead of working on many cancers, Zhang Tingdong focused mainly on leukemia. Also, instead of using a mixture of many ingredients, Zhang tested each individual component of the formula. He found that while the arsenic component is effective against leukemia, mercury chloride and cinobufagin venom toad were not, and caused renal toxicity and high blood pressure respectively. Their first paper was published in 1973, attributed to Zhang Tingdong, Pengfei Zhang, Wang Shouren, Han Taiyun at the Heilongjiang medical reports. They used "cancer injection" (also called "cancer spirit No. 1" or "Ailing-1") From 1994, the therapeutic value of intravenous pure ATO for the treatment of APL were further confirmed through clinical trials with the help of researchers from Shanghai, New York, etc. Intravenous pure As2O3 solution’s mechanism of action, pharmacokinetics and clinical efficacy of was extensively published

The development of pure oral arsenic trioxide was invented and patented in Hong Kong, China. With memories of the Fowler’s solution, an oral As2O3 formulation or the “modern” liquor arsenicalis was revived. in 2009. Oral preparation of As2O3 (oral-As2O3) was shown to be efficacious for APL in first relapse (R1), inducing second complete remission (CR2) in more than 90% of patients. Further, in an effort to prevent relapses, oral-As2O3 was used during induction and maintenance of CR1. This strategy resulted in favorable overall-survival (OS) and leukemia-free-survival (LFS). This 1&nbsp;mg/ml oral-As2O3 solution has a bioavailability comparable with that of i.v. As2O3. As of 2024, only Hong Kong uses oral arsenic to combat relapsed APL. Intravenous arsenic trioxide is used in other parts of the world. The disadvantages of intravenous arsenic trioxide treatment includes  high cost (around US$50,000 dollars per month, not including the high hospitalization cost involved) and serious cardiac toxicity.

##### Overdose 
If arsenic poisoning occurs (with the person experiencing seizures, muscle weakness, confusion), the drug should not be given anymore and appropriate treatment should be started. Penicillamine is commonly used at a dose of up to 1 g/day. For patients unable to take medicine by mouth, dimercaprol can be given through muscle injection at a dose of 3&nbsp;mg/kg body weight every 4 hours until life-threatening symptoms become less severe. In cases of coagulopathy, DMSA is used at a dose of 10&nbsp;mg/kg body weight every 8 hours for 5 days, followed by every 12 hours for 2 weeks. Kidney dialysis may also be considered.

#### Research and development 
##### Acute promyelocytic leukemia 
On the other hand, Realgar/Indigo naturalis formula (RIF) was developed in the 1980s entirely based on traditional Chinese Medicine (TCM) concepts and comprises realgar, Indigo naturalis, Salvia miltiiorrhiza and Radix pseudostellariae. Tetraarsenic tetrasulphide (As4S4), indirubin and tanshinone IIA are the active ingredients of RIF with in-vitro synergism. liver, stomach, prostate, and breast cancers, as well as gliomas and pancreatic cancer (in combination with parthenolide).

Arsenic trioxide also appears promising for treating autoimmune diseases (based on studies in mice).

## Related pages
*Arsenic tribromide
*Arsenic pentafluoride
*Bismuth trioxide
*Antimony trioxide
*Tu Youyou

## References
## Other websites
* Oral-ATO
* Arsenicum (or Pishuang)
* https://www.nature.com/articles/nm0907-1005, https://www.nature.com/articles/nm1107-1278, some history of the patent of intravenous arsenic trioxide (“Trisenox”, with patent holds by an American company)
* https://www.hk01.com/article/1101911
* https://archive.today/20250315150439/https://news.google.com/search?q=%E5%8F%A3%E6%9C%8D%E7%A0%92%E9%9C%9C%E6%B2%BB%E8%A1%80%E7%99%8C&hl=zh-HK&gl=HK&ceid=HK:zh-Hant - Archived page of Google news search (in Chinese), with “oral Pishuang cures blood cancer” as search term
* Zhang Tingdong at Pubmed

## Further reading
* 
* https://www.nytimes.com/2001/05/06/magazine/2-case-study-leukemia-location-harbin-china-chairman-mao-s-cure-for-cancer.html (archive)