More Mercury Factoids

The House of Representatives Resource Committee (RC) report on mercury leaves a trail of talking points like bread crumbs, in an attempt to lead the reader to this conclusion:

There has been no credible evidence of harm to pregnant women or their unborn children from regular consumption of fish. (page 3 of RC’s report)

However, it’s a trail that leads away, not towards enlightenment about mercury risks.

A large part of the RC’s complaint has to do with the EPA’s Reference Dose (RfD) for methylmercury. The RfD has been used to develop the fish advisory for methylmercury. It is also the benchmark used to evaluate the blood-mercury data collected during the NHANES survey. It is one of the reasons that there is such concern about health risks potentially associated with mercury emissions from power plants. The RfD for methyl mercury is based on a blood mercury level of 58 ug/L, which is the lower 95% confidence interval on an estimated dose that doubles the prevalence of young children with scores on a test of intellectual development that would fall into the clinically subnormal range. The EPA applied a 10-fold uncertainty factor to this value to obtain the RfD. So, the RfD for methylmercury is intended to protect intellectual development of children.

The complaints that the RC makes about the RfD are: 1) it is the most restrictive protective level in the world; 2) it is based on results from a single test of children that is not sensitive enough to discern effects from mercury alone; 3) the study subjects were also exposed to very high levels of toxic organic compounds like DDT and PCBs that mimic mercury’s effects and can make them worse; 4) the study is also not reflective of U.S. fish consumption (page 3 of RC’s report).

A little bit of conceptual ground clearing is needed before we deconstruct these factoids. As has been discussed on this blog, the RfD is defined as an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. The RfD is viewed as a useful reference point for gauging the potential for adverse effects at other levels of exposure.

Important qualifiers to keep in mind in thinking about the RfD are: 1) doses at the RfD (or less) are not likely to be associated with any health risks. They are likely to be protective of human health and of little regulatory concern; 2) in contrast, as the level and frequency of exposures exceeding the RfD increase, the probability of adverse effects being observed in a human population also increases; 3) the conclusion that all doses below the RfD are acceptable and that all doses in excess of the RfD are unacceptable cannot be categorically stated.

With this in mind, on to the factoids:

“It is the most restrictive protective level in the world”

An inane argument to be brought up in support of the RC’s “no credible evidence” thesis. Whether or not the RfD is restrictive isn’t terribly pertinent. Whether or not it is scientifically robust is pertinent. We discuss that point in just a moment, but it is important to note that the National Academy of Sciences (NAS) report on methylmercury endorsed the EPA’s RfD value.

“It is based on results from a single test of children that is not sensitive enough to discern effects from mercury alone”

A statement that exposes a wealth of ignorance about how studies are used to evaluate human health risks from chemical exposure. The RfD is developed from the one critical study that is well conducted and identifies the most sensitive end point of toxicity. This one study is selected from the weight of evidence for adverse effects for a chemical. Prior selecting the critical study, the accumulated studies are reviewed to make sure that the chemical in question is associated with specific adverse effects (hazard identification) and that there is evidence of a relationship between levels of exposure and frequency and/or severity of adverse effects (dose-response assessment). The NAS report says:

Chronic, low-dose prenatal MeHg exposure from maternal consumption of fish has been associated with more subtle end points of neurotoxicity in children. Those end points include poor performance on neurobehavioral tests, particularly on tests of attention, fine-motor function, language, visual-spatial abilities (e.g., drawing), and verbal memory. Of three large epidemiological studies, two studies — one conducted in the Faroe Islands and one in New Zealand — found such associations, but those effects were not seen in a major study conducted in the Seychelles islands. (Page 4, Executive Summary)

Each of these three large epidemiological studies was judged by NAS to be well designed and carefully conducted, and each examined prenatal methylmercury exposures within the range of the general U.S. population exposures. In the Faroe Islands and New Zealand studies, methylmercury exposure was associated with poor neurodevelopmental outcomes, but no relation with outcome was seen in the Seychelles study.

The NAS considered that the differences in findings between the Faroe and the Seychelles studies might be explained by differences in the study designs and in the characteristics of the study populations. These differences included the ways methylmercury exposure was measured (in umbilical-cord blood versus maternal hair), the types of neurological and psychological testing performed on children, the ages of testing between the two studies (7 years versus 5.5 years of age), and the patterns of methylmercury exposure between the two study settings. Those differences in study characteristics did not explain the differences in the findings, when the New Zealand study was included in the analysis. The New Zealand study used a research design similar to the Seychelles study. The patterns of exposure to methylmercury observed in the New Zealand study were similar to the Seychelles study. However, the New Zealand study reported associations of neurodevelopmental effects with methylmercury exposure that were similar to those found in the Faroe Islands. The NAS report goes on to say:

The committee concludes that there do not appear to be any serious flaws in the design and conduct of the Seychelles, Faroe Islands, and New Zealand studies that would preclude their use in a risk assessment. However, because there is a large body of scientific evidence showing adverse neurodevelopmental effects, including well-designed epidemiological studies, the committee concludes that an RfD should not be derived from a study, such as the Seychelles study, that did not observe any associations with MeHg.

In comparing the studies that observed effects, the strengths of the New Zealand study include an ethnically mixed population and the use of end points that are more valid for predicting school performance. The advantages of the Faroe Islands study over the New Zealand study include a larger study population, the use of two measures of exposure (i.e., hair and umbilical-cord blood), extensive peer review in the epidemiological literature, and re-analysis in response to questions raised by panelists at a 1998 NIEHS workshop and by this committee in the course of its deliberations. (Page 6 of the Executive Summary)

At the end of the day, the NAS committee concluded that the Faroe Islands study was the most appropriate study for deriving the RfD. The reasons for selecting it directly rebut the RC’s contention that “just one study” was considered (as if it is a weak reed), and an insufficiently powerful study at that. A misleading statement that appears to have been skillfully crafted.

“The study subjects were also exposed to very high levels of toxic organic compounds like DDT and PCBs that mimic mercury’s effects and can make them worse”

This appears to be an attempt to discredit the Faroe Island researchers by alleging that they failed to account for confounding factors in evaluating relationships between neurodevelopmental effects and methylmercury exposure. That wasn’t the case, however, as addressed by the NAS report:

The Faroe Islands population was also exposed to relatively high levels of polychlorinated biphenyls (PCBs). However, on the basis of an analysis of the data, the committee concluded that the adverse effects found in the Faroe Islands study, including those seen in the Boston Naming Test, were not attributable to PCB exposure and that PCB exposure did not invalidate the use of the Faroe Islands study as the basis of risk assessment for MeHg. (Page 6 of the Executive Summary)

A side point brought up by the RC’s factoid: people are not exposed to chemicals in isolation. The RfD for methylmercury, by itself, does not account for the potential for neurodevelopmental effects from multiple chemicals, such as PCBs, chlorinated pesticides (including DDT), dioxins and furans, and brominated fire retardants, and by itself, may not necessarily be protective, if there is also exposure to those other substances. Tools exist for addressing such cumulative risks – but that is a topic for another day.

“The study is also not reflective of U.S. fish consumption”

Putting aside the fact the NAS report stated that each epidemiological study examined prenatal methylmercury exposures within the range of the general U.S. population exposures, this assertion (it doesn’t really even rise to the level of factoid) belies a very narrow view of the world, or even the U.S. Fish consumers such as low-income or minority subsistence fishermen, Native Americans or hard-core recreational anglers may have typical consumption rates that are substantially higher than most Americans. While I haven’t yet done the analysis on this one yet (will I have to fact-check all of the RC’s stuff??), neither has the RC staff. These studies probably aren’t reflective of fish consumption for white upper-middle class professionals in Washington, D.C., but then again, Rep. Pombo’s aides just may need to get out a little more often.

There’s more stuff to deconstruct, but we all probably need a break. There will be more, later.