Net effects explains the benefits to children from maternal fish consumption despite methylmercury in fish.

In 2001 the U.S. Food and Drug Administration (FDA) issued precautionary advice to pregnant women to limit fish consumption over concern that the methylmercury content might harm their children's neurodevelopment. This concern was based largely on results from an epidemiological study of mothers primarily exposed to methylmercury from consuming pilot whale. Subsequently, FDA and the World Health Organization/Food and Agriculture Organization (WHO/FAO) undertook independent assessments of fish consumption that considered net effects from both fish nutrients, primarily omega-3 fatty acids, as beneficial and methylmercury as harmful. Both assessments estimated that when mothers regularly consume fish during pregnancy, their children are likely to have improved neurodevelopment compared to children of non-fish eaters despite their exposure to methylmercury. These estimated improvements included gains of two to over five full scale IQ points from levels of maternal consumption that are achievable in most of the world. Consistent with those estimates, human research on fish consumption and child neurodevelopment from more than 200,000 mother-child pairs now collectively reports 51 beneficial associations with neurodevelopmental outcomes and three adverse associations, the latter with no discernable pattern. These associations include full scale IQ gains similar to, or somewhat higher than, those estimated by FDA and FAO/WHO. Also consistent with the FDA and FAO/WHO estimates, research has reported beneficial associations with fish consumption when pregnant women are exposed to methylmercury from fish in excess of the U.S. Environmental Protection Agency's (EPA) Reference Dose (RfD). Our analysis evaluates how the net effects approach as utilized by FDA and FAO/WHO provides a holistic explanation for these results with implications for public health policy. This concordance of net effects modeling and empirical scientific evidence supports a clarification of current public health recommendations to focus on greater fish consumption by pregnant women for their children's neurodevelopment.

Estimates of the 2015 global and regional disease burden from four foodborne metals - arsenic, cadmium, lead and methylmercury.

The impact of foodborne metals on the burden of disease has been largely overlooked, in comparison to the attention on acute diseases associated with infectious foodborne agents. Four articles in this special section describe in detail the burden of disease from foodborne lead, methylmercury, arsenic, and cadmium. Ingested lead and methylmercury are causally associated with lifelong intellectual disability. Long term ingestion of arsenic is causally associated with an increased risk of cancer. Long term ingestion of cadmium is causally associated with an increased risk of late stage chronic kidney disease. This article presents an overview of the burden of disease from these four foodborne metals and discusses them in the context of the World Health Organization's initiative to estimate the global burden of foodborne disease. The results indicate that in 2015, ingestion of arsenic, methylmercury, lead, and cadmium resulted in more than 1 million illnesses, over 56,000 deaths, and more than 9 million disability-adjusted life years (DALYs) worldwide. The greatest impact on DALYs was in the Western Pacific B subregion. All of the metals were found to have high DALYs per case in comparison with other foodborne disease agents, including infectious and parasitic agents. In addition, lead, arsenic, and methylmercury were found to have high DALYs per 100,000 population in comparison to other foodborne disease agents.

Global burden of intellectual disability resulting from dietary exposure to lead, 2015.

Lead is a ubiquitous dietary contaminant that occurs in food because of natural and anthropogenic sources and pathways of exposure. Lead adversely affects a number of tissues and organ systems and the severity of effect on each is dependent on the level and duration of exposure. The most sensitive and notable effects are those that occur on the nervous system. This is particularly the case in the exposure to the fetus, infant and child. Infants and children generally have higher lead exposures on a body weight basis. While lead exposure can come from many sources, a major source of exposure for at least some individuals comes from food. Estimates for the impact of dietary lead on IQ were developed from published total diet studies. While most of these were designed to characterize intake of chemical contaminants on a national basis, some sampled market baskets from a single city. To develop global estimates, default ranges were created for countries with no data which encompassed the values encountered elsewhere. Blood lead levels and IQ decrements were estimated using functions previously developed by the WHO Joint Expert Committee for Food Additives. Since both the exposure and dose response components were variable and uncertain, a two dimensional Monte-Carlo simulation was used to develop the estimates for the impact of dietary lead on IQ. In addition to estimating blood lead and IQ decrements attributable to dietary lead from those countries with published market basket data, simulations were also run for WHO regions that sampled in the variability dimension based on the population size of the individual countries in each region. Dietary exposure to lead occurs throughout the world. The global average IQ decrement attributable to dietary lead was 1.1. The total number of Disability-Adjusted Life Years (DALYs) arising from those IQ decrements were estimated to be 5.2 million DALYs, with an uncertainty range of 0-31 million DALYs. Significant uncertainties regarding exposure and dose-response relationships, however, warrant continued investigation.

The limits of regulatory toxicology.

The Acceptable Daily Intake (ADI) has been used by regulatory and public health organizations (e.g., the U.S. Food and Drug and Administration, and the World Health Organization) for chemicals for more than 50 years. The ADI concept was also initially employed at the U.S. Environmental Protection Agency at its inception in 1971, although with the adoption of newer terminology, it later became known as the Reference Dose (RfD). It is clear from the literature that both were first devised as instruments of regulatory policy. In the intervening years, it has become common to use language that implies that these standards are statements of scientific fact. Similarly, some of the discretionary or default values that are used to derive regulatory standards are represented as scientific assumptions when in fact they also represent regulatory policy. This confusion impedes both the best use of the available science and informed public participation in policy making. In addition, the misconception of the ADI or the RfD as statements of scientific fact may impede the consideration of alternative means to reduce exposure to chemicals that may be harmful, including regulatory measures that do not involve prescribing a regulatory concentration limit.

Update of US FDA's Total Diet Study food list and diets.

The US Food and Drug Administration's (FDA) Total Diet Study (TDS) has been conducted continuously since the early 1960s to measures levels of various pesticide residues, contaminants, and nutrients in foods and to estimate the dietary exposures to these compounds. Both the TDS food list and the consumption amounts used for estimating exposures are based on results of nationwide food consumption surveys, and they are updated periodically to reflect changes in food consumption patterns. The most recent update was completed in 2003 using the same methodology employed in the previous update (1990). The updated food list includes approximately the same number of foods (285) as the previous list (290). Although most (75%) foods are the same in both versions, the new list reflects trends in consumption of foods containing less fat. The updated diets reflect an increase in total food consumption, with most notable increases in consumption of grains and beverages. A case study comparing cadmium exposures calculated from both the 1990 and 2003 versions of the TDS demonstrated the potential impact of changes in both the food list and consumption amounts on TDS exposure estimates.

An exposure assessment for methylmercury from seafood for consumers in the United States.

An exposure model was developed to relate seafood consumption to levels of methylmercury (reported as mercury) in blood and hair in the U.S. population, and two subpopulations defined as children aged 2-5 and women aged 18-45. Seafood consumption was initially modeled using short-term (three-day) U.S.-consumption surveys that recorded the amount of fish eaten per meal. Since longer exposure periods include more eaters with a lower daily mean intake, the consumption distribution was adjusted by broadening the distribution to include more eaters and reducing the distribution mean to keep total population intake constant. The estimate for the total number of eaters was based on long-term purchase diaries. Levels of mercury in canned tuna, swordfish, and shark were based on FDA survey data. The distribution of mercury levels in other species was based on reported mean levels, with the frequency of consumption of each species based on market share. The shape distribution for the given mean was based on the range of variation encountered among shark, tuna, and swordfish. These distributions were integrated with a simulation that estimated average daily intake over a 360-day period, with 10,000 simulated individuals and 1,000 uncertainty iterations. The results of this simulation were then used as an input to a second simulation that modeled levels of mercury in blood and hair. The relationship between dietary intake and blood mercury in a population was modeled from data obtained from a 90-day study with controlled seafood intake. The relationship between blood and hair mercury in a population was modeled from data obtained from several sources. The biomarker simulation employed 2,000 simulated individuals and 1,000 uncertainty iterations. These results were then compared to the recent National Health and Nutrition Examination Survey (NHANES) that tabulated blood and hair mercury levels in a cross-section of the U.S. population. The output of the model and NHANES results were similar for both children and adult women, with predicted mercury biomarker concentrations within a factor of two or less of NHANES biomarker results. However, the model tended to underpredict blood levels for women and overpredict blood and hair levels for children.