Arsenic is notoriously poisonous and may also be an essential element in ultratrace amounts. During World War I, both sides used "arsenic-based sneezing and vomiting agents …to force enemy soldiers to remove their gas masks before firing mustard or phosgene at them in a second salvo." It has been used as a pharmaceutical agent since antiquity, including for the treatment of syphilis before the development of antibiotics. Arsenic is also a component of melarsoprol, a medicinal drug used in the treatment of human African trypanosomiasis or sleeping sickness. In 2003, arsenic trioxide (under the trade name Trisenox) was re-introduced for the treatment of acute promyelocytic leukaemia, a cancer of the blood and bone marrow. Arsenic in drinking water, which causes lung and bladder cancer, has been associated with a reduction in breast cancer mortality rates.