Is is appropriate to use a semicolon in order to avoid comma ambiguity in sentences like the following?
When they returned from the zoo; Charles, James, and Jane looked for new locations to visit.
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Punctuation is mostly a matter of style, and while there a few rules that all style guides agree upon (e.g, a period after a declarative sentence), you should consult your own style guide, either the one you've chosen or the one thrust upon you.
I use The Chicago Manual of Style, which recommends semicolons in the following cases
The day was hot and still[;][ and] I decided to take a nap.
The day was beautiful; however, I decided to take a nap anyway.
Queen Victoria was known as the grandmother of Europe because many of her descendants become royal heads of state including Alexandra, Tsarina of Russia; Wilhelm II, Kaiser of Germany; and Victoria Eugenie, Queen of Spain.
It's not appropriate to use a semicolon after a subordinate clause. I understand that you're thinking you have too many commas, but the correct sentence is
"When they returned from the zoo, Charles, James, and Jane looked for new locations to visit."
From Purdue OWL: 2. Use commas after introductory a) clauses, b) phrases, or c) words that come before the main clause.
a. Common starter words for introductory clauses that should be followed by a comma include after, although, as, because, if, since, when, while.
While I was eating, the cat scratched at the door. Because her alarm clock was broken, she was late for class. If you are ill, you ought to see a doctor. When the snow stops falling, we'll shovel the driveway.