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: The following factors appear to predispose to the development of this complication : abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia , and epidural cerebrospinal leakage ; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults ; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents ; and the use of methotrexate diluents of unphysiologic pH , ionic content and osmolarity .
### Output Text:
The following factors appear to predispose to the development of this complication : abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia , and epidural cerebrospinal leakage ; elevated cerebrospinal fluid <span class="chemical">methothexate</span> concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high <span class="chemical">methotrexate</span> doses based on body surface area calculations in older children and adults ; the presence of neurotoxic preservatives in commercially available <span class="chemical">methotrexate</span> preparations and diluents ; and the use of <span class="chemical">methotrexate</span> diluents of unphysiologic pH , ionic content and osmolarity . 