D.H. Lawrence’s poem "New Heaven and Earth" describes the English poet’s delight when experiencing and fathoming the “unknown unknown.” Tuesday’s symposium session, "Unknown, Unknowns: Exploring the Unidentified Fraction of Complex Mixtures," featured mixtures experts who take equal delight in the exploration of mixtures toxicity, including unknown fractions. For those of us involved in the design or assessment of chemical-intensive products or formulations, mixtures assessment does not invoke delight, but instead dread because there are few easily accessible mixtures assessment paradigms or models.
Do unknowns matter and is it necessary to consider chemical interactions? Jane Ellen Simmons communicated why toxicologists need to appreciate the role that mixtures and unknowns play in affecting the toxicity of a product; for example, smoking and asbestos increase the relative risk of lung cancer by a factor of five when exposure occurs concurrently. Besides the toxic interactive effects of “knowns,” there is cause to be concerned over the presence of “unknowns,” such as the 100,000 uncharacterized substances in cigarette smoke or complex hydrocarbon mixtures.
Dean Jones presented his research in which known metabolic pathways are used to identify unknowns. Instead of starting with a series of known chemicals, biological activity is predicted by starting with metabolic pathways. Such automated metabolomics systems (including one with the memorable name mummichog, which is American Indian term for groups, and is also name of a small fish that live in groups) can someday be used to assess collective activity of complex mixtures, including uncharacterized fractions.
The mixtures work presented in the symposium indicates that the bulk of mixtures research is still in the theoretical phase, with much work left to be done before mixtures tools are used on a regular basis to inform decisions pertaining to hazard identification or risk assessment. I am hopeful that as these tools are made more accessible, there will be less dread when assessing mixtures!