Yes, metabolic intermediates can be harmful. During the metabolic activation of certain compounds, reactive intermediates may form, which can bind covalently to cellular macromolecules such as DNA, proteins, or lipids, leading to cellular damage. For example, the intermediate N-acetyl-p-benzoquinone imine (NAPQI) formed from acetaminophen metabolism is highly reactive and can cause liver damage if not sufficiently detoxified.