The Syrian regime's air force used the chemical weapon chlorine in an attack on the town of Saraqib in 2018, the global toxic arms watchdog said on Monday after an investigation.
The report is the second by an investigations team set up by the Organisation for the Prohibition of Chemical Weapons (OPCW), which has the new power to apportion blame for attacks.
The OPCW said in a statement that the Investigations and Identification Team (IIT) "concludes that units of the Syrian Arab Air Force used chemical weapons in Saraqib on 4 February 2018".
Reactions from abroad were swift, with France and Germany warning the findings would not go unanswered.
"The use of these arms by the Syrian regime, documented and irrefutable, is unacceptable," said French foreign minister Jean-Yves Le Drian said, calling for an "appropriate response" from the international community.
His German counterpart Heiko Maas said "those responsible must be held accountable", adding: "For us, it is clear that such an obvious violation of international law cannot remain without consequences."
"There are reasonable grounds to believe that, at approximately 21:22 on 4 February 2018, a military helicopter of the Syrian Arab Air Force under the control of the Tiger Forces hit eastern Saraqib by dropping at least one cylinder," the OPCW report said.
"The cylinder ruptured and released chlorine over a large area, affecting 12 named individuals."
OPCW investigators interviewed 30 witnesses, analysed samples collected at the scene, reviewed symptoms reported by victims and medical staff and examined satellite imagery to reach their conclusions, the Hague-based organisation said.
Symptoms "included shortness of breath, skin irritation, chest pain, and coughing", the report said.
However, it added that it "regrets" that the Syrian regime refused to grant access to the site, some 30 miles (50 kilometres) south of Aleppo, despite repeated requests.
Damascus and its allies have claimed that chemical attacks had been "staged" in Syria in order to incriminate the regime, a hypothesis ruled out by investigators in Monday's report.
"Several leads were followed in this respect," IIT coordinator Santiago Onate Laborde said in a statement on the OPCW website.
"However, these leads were not supported by any concrete evidence, and the IIT -- despite numerous attempts -- was unable to corroborate these hypotheses."
The team issued its first report a year ago, in which it said that Syrian President Bashar al-Assad's air force used the nerve agent sarin and chlorine in two attacks on the village of Lataminah in March 2017.
Despite strong objections by Damascus and its ally Moscow, OPCW member states voted in 2018 to set up the team to attribute blame for attacks. Previously the watchdog could only say if chemical attacks had happened or not.
Syria has continued to deny the use of chemical weapons and insists it has handed over its weapons stockpiles under a 2013 agreement, prompted by a suspected sarin attack that killed 1,400 people in the Damascus suburb of Ghouta.
But OPCW investigators said they believed that orders for the 2018 Saraqib attack must have come from above, and that there was no indication that "rogue elements or individuals" were responsible.
"The IIT obtained information from various sources suggesting that, for chemical weapons to be used in the manner described above, orders would be required," the report on the attack said.
While it had not identified a "specific chain of command", the Syrian military general command appeared to have "delegated decisions on the use of chlorine to "operational level commanders", the OPCW said.
OPCW member states will vote later this month on whether to impose sanctions on Syria, including the suspension of its voting rights in the organisation, over its failure to comply with its rules.
The OPCW's governing body has told Syria it must declare all details about the facilities used to produce the sarin and chlorine used in the 2017 attacks.
Western powers have expressed concern that Damascus has failed to declare and destroy all its chemical weapons under the 2013 deal.
The OPCW chief said in March there were still gaps and inconsistencies in Syria's reports to the body.
The United Nations said in March that Damascus had for years failed to reply to a series of 19 questions about its weapons installations, which could have been used to stock or produce chemical weapons.