Table open cache too small

Table Open Cache (table_open_cache, old table_cache) is the number of open tables (Open_tables) for all threads. Increasing table_open_cache increases the number of file descriptors (open_files_limit) that MySQL requires.
You can check whether you need to increase the table open cache by checking Open_tables and Opened_tables. If the value of Opened_tables is large and you do not use FLUSH TABLES often (which just forces all tables to be closed and reopened), then you should increase the value of the table_open_cache variable.

See also MySQL Documentation.