It is also understood that at least five officers were attempting to restrain Ibrahima Sey, 29, at a police station in east London in March, when he was sprayed with the incapacitant.
News that CS was used while a man was handcuffed brought calls for trials of the spray, which is being tested by 16 police forces in England and Wales, to be halted immediately.
Ghanaian-born Mr Sey, who suffered from mental problems, was arrested after a fracas involving his wife and two children.
Initial findings of the police inquiry into the death at Ilford police station, in east London, are understood to have found that Mr Sey was handcuffed at the time he was sprayed, and was struggling, but contrary to some reports he was not head butting officers. Sources suggest that shortly before the struggle he attempted to kiss a woman police officer.
A friend of Mr Sey, Paebou Ndimbalan, who had travelled with him to the station in a police van, has claimed that up to 12 officers were involved in his arrest and restraining him at the police station.
Tony Banks, Labour MP for Newham North West, said yesterday: "If he was restrained already with handcuffs to use CS spray is dangerous and reckless - it must be outside the permitted rules and guidelines.
"The CS sprays should be withdrawn immediately from service until this matter is resolved."
CS spray, which causes breathing difficulties, streaming eyes and nose, is designed to be used defensively to restrain violent people.
A post-mortem examination showed that Mr Sey, who was 6ft 3 and weighed 18 stones, collapsed after a period of exertion and was suffering from hypertensive heart disease. Death was not a result of being sprayed, however further toxicology tests are being carried out on his brain to see whether it was a contributing factor.
Police from Forest Gate station in east London were called to Mr Sey's home in Forest Gate at 4.24am on 16 March, where they found his wife standing in the road. She had jumped from their first floor flat. Mr Sey was allegedly holding his six month old baby and shouting through an open window.
Mr Ndimbalan eventually persuaded Mr Sey to get into the back of a police van with him. When they arrived at the police yard of Ilford station the two men were separated.
A scuffle took place in which Mr Sey was handcuffed. Shortly afterwards he was sprayed in the face, during which several people suffered from the effects of the incapacitant and were replaced by other officers.
Mr Sey was placed in a cell and subsequently complained of feeling unwell. He was taken to hospital where he later died.
An inquiry is being led by Frank Wilkinson, Assistant Chief Constable of Hertfordshire police, and the case is being overseen by the independent Police Complaints Authority.
The Newham Monitoring Project, a campaign group, is calling for a halt to the CS trial and for the officers involved to be suspended while an independent inquiry is set up. Project spokesman Piara Powar said: "When CS spray first came out it was said it was for use on dangerous criminals, not for people handcuffed inside a police station."
Lee Jasper, for the National Black Caucus, added: "How can it possibly be justified to use CS spray on a suspect who is handcuffed and surrounded by officers in the confines of a police station?"