Puffball mushrooms are bioaccumulators. This means they absorb toxins from the material or environment they are growing in. Puffballs growing near highways absorb fumes and other chemicals you probably don't want to ingest. Be cautious where you forage puffballs, and you'll be fine. Of course, always, always, check the inner flesh to make sure it is pure white. Even the slightest bit of yellowing will cause stomach upset.