Hair Analysis Panel Discussion: Section 4.3

Section 4
4.3 Reference/Background Ranges

Discussions regarding reference ranges focused on uncertainties associated with levels of metals, etc., in "healthy" or "unexposed" individuals and the variability of reference ranges used by different laboratories. The panelists discussed how the uncertainties play out when one tries to interpret results of hair analysis.

Individual comments regarding currently available reference range data and inherent limitations are detailed below:

The panelists discussed the importance of first clearly defining the term "reference range." Two panelists expressed concern about using the term synonymously with "normal" because it implies that knowledge exists about associated health status, when in fact such information is largely unavailable. Reference ranges do not represent "background" or "controls," nor do we know baseline levels for "normal" states of health (SS). We do not know what should be present in "healthy" hair (LW). Others suggested that it is background data that is ultimately being sought, noting that possible geographic and demographic differences need to be considered.

A "normal" range does not exist for many elements. Unlike drugs, the presence of which would be considered "abnormal," normal ranges need to be identified for metals. Building the database of normal levels would help assessors better understand and interpret hair analysis results. Considering hair data in the absence of reference data against which to compare them is therefore of limited utility (RB).

The availability of a reference range does not mean we know the background or typical levels of endogenous incorporation. It does not necessarily represent what occurs naturally. It may represent external exposures to ubiquitous levels of contaminants (e.g., lead dust, etc.) (MK, TC). For ATSDR's purposes, the key is distinguishing site exposures from non-site exposures (e.g., What are background levels where no known external exposure sources exist?). For example, will we be able to discern whether levels of a contaminant of interest are elevated in a potentially exposed population (LW)?

DiPietro et al. (1989) reported analytical results for 271 adults, ages 20 to 73 years, for selected elements. In comparing the findings of this study with mean hair concentrations of the same elements reported by others, investigators concluded that results compare relatively well, given limitations and variability in hair analysis (DP).

It might be useful to draw a distinction between essential trace elements and non-essential trace elements. One would expect a reference level of the essential trace elements in hair. The presence of non-essential elements, on the other hand, would suggest environmental exposure, deposited internally or externally (TC).

According to two panelists, available reference ranges are often biased and based on small numbers. Some reference ranges are based on one or two old case reports (RB, MG).

The validity of samples used to develop a reference range in the first place is unknown (RB).

Available reference values may not relate to the population under study (RB).

Reference ranges with an approximate 100-fold difference have been used by different commercial laboratories. What does this really mean from a biological perspective? (SS)

One panelist emphasized that more important than understanding reference ranges is gaining an understanding of whether chemical-specific value have toxicologic or clinical significance. The availability of reference range information alone is inadequate to assess the clinical significance of a particular laboratory result; the fact that a reference range has been exceeded does not establish that the individual sustained a toxicologically significant dose (MK). Another panelist reminded the group that establishing reliable reference levels will inform assessors about the possible extent of exposures (LW).

One panelist questioned whether CDC might consider additional hair analysis as part NHANES efforts—providing an opportunity to collect data on a cross section of the population. It was speculated that if the science supported the need for such data collection, it could be proposed (funding aside) (LW, DP). NHANES 99+ did measure hair mercury of a selected subpopulation (children ages 1 to 5 and females 16 to 49 years) (CDC 2001a).

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