The cloud of nitrobenzene escaped after an accident at a chemical plant belonging to the firm Clariant in an industrial park near the Höchst district of the city.
The leak was only stopped after half an hour, a spokesman for the Frankfurt fire brigade said, adding that measurements outside the park suggested there were no immediate health risks.
Nevertheless, a spokesman for the industrial park operator Infraserv said the cloud drifted over the Höchst and Unterliederbach districts, where residents were told to stay at home and keep doors and windows shut during the afternoon. Police also closed off the centre of Höchst and shut down a local railway station. Many people in the area were seen holding their hands or cloth in front of their mouths.
The all-clear was only given in the early evening.
Nitrobenzene, a substance used in the production of car paint, is considered highly dangerous if breathed in or swallowed, and can easily be absorbed through the skin. It is also considered carcinogenic and prolonged exposure can damage the liver, lungs, and central nervous system.
Both the cause of the accident and the exact quantity of the chemical released were not initially revealed, though the Infraserv spokesman spoke of a "small amount." The fire brigade sprayed water onto the chemical in an attempt to contain the leak.