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Medical relief organisation Syrian American Medical Society (SAMS) said 41 people had been killed, with other reports putting the death toll much higher. The civil defence rescue service, which operates in rebel-held areas of Syria, put it as high as 150 in a report on one of its Twitter feeds.
The Russian-backed Syrian state denied government forces had launched any chemical attack as the reports began circulating on Saturday night and said rebels in the eastern Ghouta town of Douma were in a state of collapse and spreading false news.
Reuters could not independently verify the reports.
The lifeless bodies of around a dozen children, women and men, some of them with foam at the mouth, were shown in one video circulated by activists. "Douma city, April 7 ... there is a strong smell here," a voice can be heard saying.
The U.S. State Department said reports of mass casualties from an alleged chemical weapons attack in Douma were "horrifying" and would, if confirmed, "demand an immediate response by the international community".
President Bashar al-Assad has won back control of nearly all of eastern Ghouta in a Russian-backed military campaign that began in February, leaving just Douma in rebel hands. After a lull of days, government forces began bombarding Douma again on Friday.
The offensive in Ghouta has been one of the deadliest of the seven-year-long war, killing more than 1,600 civilians according to the Syrian Observatory for Human Rights.
The Observatory said it could not confirm if chemical weapons had been used in the attack on Saturday.
Observatory Director Rami Abdulrahman said 11 people had died in Douma as a result of suffocation caused by the smoke from conventional weapons being dropped by the government. It said a total of 70 people suffered breathing difficulties.
Medical relief organisation SAMS said a chlorine bomb hit Douma hospital, killing six people, and a second attack with "mixed agents" including nerve agents had hit a nearby building.
Basel Termanini, the U.S.-based vice president of SAMS, told Reuters another 35 people had been killed at the nearby apartment building, most of them women and children.
SAMS operates 139 medical facilities in Syria where it supports 1,880 medical personnel, according to its website.
"We are contacting the U.N. and the U.S. government and the European governments," he said by telephone.
Syrian state news agency SANA said the rebel group in Douma, Jaish al-Islam, was making "chemical attack fabrications in an exposed and failed attempt to obstruct advances by the Syrian Arab army," citing an official source.
U.S. State Department spokeswoman Heather Nauret recalled a 2017 sarin gas attack in northwestern Syria that the West and the United Nations blamed on Assad's government.
"The Assad regime and its backers must be held accountable and any further attacks prevented immediately," she said.
"The United States calls on Russia to end this unmitigated support immediately and work with the international community to prevent further, barbaric chemical weapons attacks," Nauert said in a statement.
The Syrian government has repeatedly denied using chemical weapons during the conflict.