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As far as I know, those two are the only exceptions. Is there a particular reason for this?

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The Diccionario Panhispánico de dudas says that "Santo" must be used with Domingo, Tomás, Tomé and Toribio. (Thanks Gonzalo Medina for pointing this out)

The reason to prefer to use "Santo" is to avoid confusion in oral speech. Quoting a WordReference thread:

Technically, any male saint, or "santo", could be called "Santo", and it would not be strictly wrong (although it would be very uncommon) to say "Santo Pedro" or "Santo Juan". However, the custom for male saints is to abbreviate the title "Santo" to "San".

The exception to this rule is when the first syllable of the name is "To" or "Do". Under those circumstances, if one said "San Tomás", it would be unclear whether the man's name was Tomás or just "Mas" -- because you could be saying "Santo Mas". In the same way, if you said "San Domingo", it would sound very much like "Santo Mingo", and again confusion would result.

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    The Diccionario panhispánico de dudas: buscon.rae.es/dpdI/SrvltGUIBusDPD?lema=santo says that only santo must be used for Domingo, Tomás, Tomé, and Toribio. – Gonzalo Medina Jan 16 '12 at 0:31
  • On the other hand, it's a silly rule. What if they invented another saint called "Toño" (or you want to called that way a "Antonio"), "Tobaldo" or "Tontolín". You keep the same problem with the pronuntiation as in "Tomás" or "Toribio". As native speaker, I would say "Santo Tobaldo", "Santo Toño" y "Santo Tontolín" cause sound better, but "San Tontolín" is not bad either. – Ricardo Jan 16 '12 at 8:58
  • @Ricardo: every rule is silly to a certain extent and on a certain level ;-) – Gonzalo Medina Jan 16 '12 at 18:23
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    Maybe, but I live in San Jose, CA and there are streets and an expressway named San Tomas and San Tomas Aquino (Tomas pronounced by everybody in the Spanish fashion, not like "Thomas"). So the rule is not observed here. – Marc Sep 21 '18 at 22:13
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    I'm curious why santo is retained for these four and not for any other male saints beginning To-/Do- e.g. San Doroteo, San Torpetes, San Torcuato etc. – ukemi Sep 23 '18 at 9:21
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As dusan says, the reason for the cacophonous lack of apocope is to avoid ambiguity in interpreting the saint's name:

  • San Tomé = /ˈsantoˈme/ = Santo Me
  • San Tomás = /ˈsantoˈmas/ = Santo Mas
  • San Toribio = /ˈsantoˈribjo/ = Santo Ribio
  • San Domingo = /ˈsandoˈmingo//ˈsantoˈmingo/ = Santo Mingo

Traditionally these are the only four saints treated as such, but there are others with an initial unstressed To-/Do-. Some of these would not require such a rule because the break is mid-syllable and would leave an unpermitted onset consonant cluster (e.g. San Torpetes, San Torcuato), but others have similar phonetic contexts to the four above, yet are not treated as such, possibly due to them simply being less popular (e.g. San Doroteo).

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