In the sentence extracted from biomedical literature, identify all the chemical entities. The required answer format is the same sentence with HTML <span> tags to mark up specific entities. 
### Entity Markup Guides:
Use <span class="chemical"> to denote a chemical.

### Input Text: These observations support the hypothesis that treatment with high doses of D - pen may induce a fibroproliferative response in rat aorta , possibly by an inhibitory effect on the cross - linking of collagen and elastin .
### Output Text:
These observations support the hypothesis that treatment with high doses of <span class="chemical">D - pen</span> may induce a fibroproliferative response in rat aorta , possibly by an inhibitory effect on the cross - linking of collagen and elastin . 