In spacecraft life support systems which are partially or fully closed, the air and water systems have sufficient interaction that contaminants in one system may become contaminants in the other. Life support system designers typically consider these media separately. In order to develop plausible and appropriate drinking water contaminant standards for longer-term NASA space missions, we performed a human health risk characterization using toxicological and exposure values typical of space operations and crew. It showed that the greatest waterborne health concern was from acute microbial infection leading to incapacitating gastrointestinal illness. While substantial data gaps exist for toxicities and exposures, ingestion exposure pathways for toxic materials yielded de minimus acute health risks unlikely to affect SEI space missions. Risks of chronic health problems from the relatively short exposures of expected space missions were within acceptable public health limits. A discussion of the interactions between the air and water subsystems in a closed life support system, and the effect on a risk characterization such as this is included.Our analysis indicates that current Space Station Freedom maximum contamination levels may be unnecessarily strict. We propose alternative drinking water contaminant values consistent with both acceptable short and long-term crew health safety. Since spacecraft drinking water treatment hardware designs are based on achieving drinking water contaminant goals, simplification of those goals allows for reconsideration of treatment designs. Consideration should be given to an integrated design for the air and water life support systems that encompasses protection for cross-media contamination.