On MacOS an extended attribute com.apple.metadata:com_apple_backup_excludeItem
is used to tell backup software that the particular file does not need to be backed up. This is a more robust solution compared to separately maintained global exclusion list as the metadata is kept physically close to the the data it describes; that way applications, who have much better idea about how to manage their files, can decide what gets backed up and what is transient and shall be skipped.
Example:
myimac:~ me$ touch testfile
myimac:~ me$ ls -alt@ testfile
-rw-r--r-- 1 me staff 0 Jul 10 12:38 testfile
myimac:~ me$ tmutil addexclusion testfile
myimac:~ me$ ls -alt@ testfile
-rw-r--r--@ 1 me staff 0 Jul 10 12:38 testfile
com.apple.metadata:com_apple_backup_excludeItem 61
myimac:~ me$ tmutil removeexclusion testfile
myimac:~ me$ ls -alt@ testfile
-rw-r--r-- 1 me staff 0 Jul 10 12:38 testfile
myimac:~ me$
For more info see man tmutil
Time Machine honors that flag, as does CrashPlan and even Arq.
Duplicacy should too.