I had that happen and the problem was one person was having their email forwarded to a pop email account. The pop got full and would reject the forwarded email. The IMS would continue to try and send it, which would clog up the queue. Then others would show "Host Unreachable". Once I turned off forwarding on the problem user, the queue cleared out and all was good. Another time I had a similiar issue, the problem was a DNS server.
Good Luck List Charter and FAQ at: http://www.sunbelt-software.com/exchange_list_charter.htm