Aidan O’Brien says he was “left with no choice” but to withdraw all four of his horses from Sunday’s Prix de l’Arc de Triomphe in Paris.
They tested positive for a banned substance, which is suspected to have been in a batch of contaminated feed.
The Irish trainer was due to run Mogul, Japan, Serpentine and Sovereign in Europe’s richest race, which Enable is bidding to win for a record third time.
His sons Joseph and Donnacha also withdrew horses from Sunday’s fixture.
A total of 11 horses trained by the O’Brien family will be absent from the meeting, with Aidan saying the decision was taken after consulting the powerful Coolmore ownership team.
“Everybody met and the lads had a good chat. To protect the integrity of racing we felt we had no choice but to withdraw the horses,” he told Racing TV on Sunday.
“The ramifications and costs are shocking. They put in so much to try make it happen, I’m just so sorry for the lads.”
A statement from O’Brien’s Ballydoyle Racing on Saturday said urine samples taken from Sunday’s runners had returned positive from a French laboratory.
“There is a possibility that the contaminant may have left their system by the time of racing on Sunday, however we have no guarantee of this,” it said.
British trainer Roger Varian, who had been using the same feed supplier – GAIN Equine Nutrition, withdrew his seven intended runners from meetings on Saturday.
In a statement on Sunday, the company said it was “hugely disappointed” for its customers in the Republic of Ireland, the UK, France and elsewhere.
“Intensive testing of our equine feed ranges, batches and individual ingredients has been underway around the clock since this issue first emerged in France,” it said.
“We are continuing to work closely with all appropriate agencies, including the Irish Department of Agriculture, to fully investigate the source, nature and extent of this contamination.
“We are also in close contact with horse racing regulatory bodies.”
On Friday night the likelihood of Aidan O’Brien’s runners competing at the ParisLongchamp fixture was thrown into doubt.
France Galop announced five horses had tested positive for the prohibited substance Zilpaterol, which was suspected to have been in contaminated food for the animals.
O’Brien’s two runners in France on Saturday were allowed to race after urine samples sent to the Irish Equine Centre came back clear.
But his contenders for the Arc had yet to be given the go-ahead, and the withdrawals will cast a cloud over a hugely anticipated fixture.
O’Brien’s Arc favourite Love was pulled out earlier in the week after heavy rain left the official going as very soft.
The absence of his quartet leaves Enable, the mount of Frankie Dettori for British trainer John Gosden, facing 10 rivals – with the field reduced from 15 to 11. She is now the general evens favourite to gain a historic success.
O’Brien has also taken St Mark’s Basilica out of the Prix Jean-Luc Lagardere as horses trained by the family were withdrawn from a total of three other Group One races.
Joseph O’Brien was due to saddle leading contender Pretty Gorgeous in the Prix Marcel Boussac, while Fancy Blue will miss the Prix de l’Opera for Donnacha.