Townsend has included uncapped props Murray McCallum and D’arcy Rae in his 40-man squad along with Newcastle pair Scott Lawson and Jon Welsh, who are back after several years out of the reckoning.
Fraser Brown misses out after a series of concussions and Edinburgh prop Simon Berghan is suspended for Scotland’s opener against Wales on February 3 after being given a six-week ban for stamping on the Glasgow hooker’s head.
Zander Fagerson, WP Nel, Ross Ford, Allan Dell, Al Dickinson and Darryl Marfo are also missing from Townsend’s front-row options. Stuart McInally is likely to keep his place at hooker with George Turner as cover and London Irish prop Gordon Reid provides some experience with 27 caps to his name.
Townsend said: “Every country going into the Six Nations is going to have injuries. It’s something you deal with. We know we have a couple of injuries in the front row so it’s down to other players to go out there and play well with Scotland.”
When asked how much of a challenge it would be to get his front row up to speed for the Cardiff encounter, he said: “On paper it’s a challenge but we’ve got evidence from November that players did very well in training and they took that into the games. Darryl Marfo and Jamie Bhatti were uncapped going into November and both played very well.
“We have two uncapped players and it’s now up to them to show us they should be picked against Wales and, if they are, go and grab that opportunity. They have got some players around them that they can learn from, but we believe in them with the ability they have shown over the last few weeks.
“D’arcy we know better as a coaching group because we worked with him at Glasgow, Murray has really come to the fore in the last few weeks at Edinburgh because he has been given an opportunity there. They can take that form into the international arena.”
Hooker Lawson, 36, won the last of his 46 caps in 2014.
Townsend said: “Scott’s experience we believe will really help us, in the hooking department given George Turner just has a couple of caps, but also with the new guys coming in at loosehead and tighthead.
“In addition to that, the way Scott has played this season, really fits with what we want to do with our game. He is dynamic, he’s a low tackler, and he’s got excellent set-piece accuracy.”
Edinburgh backs Blair Kinghorn and Nathan Fowles complete a quartet of uncapped players while Townsend has a range of options not available to him during November.
Richie Gray, Mark Bennett, Duncan Taylor and Reid have all recently made comebacks from lay-offs while Greig Laidlaw is back in full training for Clermont Auvergne.
In-form Worcester forward David Denton is set for his first cap since 2016 after a series of injuries and Stuart Hogg is included after recovering from hip and foot injuries, although he has not featured since for Glasgow.