Longitudinal study of daily intake and excretion of lead in newly born infants.

As an adjunct to a study of lead mobilization during pregnancy and lactation, we have obtained estimates of the daily lead intake and excretion/intake for 15 newly born infants monitored for at least 6 months postpartum. The longitudinal data presented reflect the far lower levels of environmental contribution to lead in blood in the 1990's than that in the earlier studies from the 1970's and early 1980's, the last period for which such dietary information is available in newly born infants. Infants were breast-fed or formula-fed or both and, in the second quarter, were usually fed solid foods (beikost). Lead concentrations were as follows: lead in breast milk, ranged from 0.09 to 3.1 microg/kg with a geometric mean of 0.55 microg/kg, lead in infant formula ranged from 0.07 to 11.4 microg/kg with a geometric mean of 1.6 microg/kg, and lead in beikost ranged from 1.1 to 27 microg/kg with a geometric mean of 2.9 microg/kg. Daily lead intakes ranged from 0.04 to 0.83 microg/kg body weight/day with a geometric mean of 0.23 microg Pb/kg body weight/day, and excretion/intake ranged from 0.7 to 22 with a geometric mean of 2.6. There was no significant difference at the 5% level in lead concentration in daily intakes and excretion/intake for the first quarter versus the second quarter for this small number of subjects. Assuming that there was no contribution from environmental samples such as house dust and ambient air, the contribution of diet to blood has been estimated from lead isotopic measurements with the following ranges: for breast milk only as the dietary source, 40 to 65%; for breast milk and infant formula as the dietary sources, 15 to 70%; and for infant formula and beikost, 20 to 80%. The geometric mean value of the dietary contribution to blood over the 6-month period of approximately 35% is consistent with earlier estimates of uptake of lead in blood in newly born infants when environmental lead concentrations were much higher. Other sources such as air, soil, and dust are considered to contribute minimally to blood lead in these infants because of the low 206Pb/204Pb ratios in environmental media. Thus, we consider that the increased excretion over intake, along with other evidence, reflects mobilization of infant tissues arising especially from rapid bone turnover at this stage of life; the tissue lead has been identified isotopically in urine.

Dietary intakes of selected elements from longitudinal 6-day duplicate diets for pregnant and nonpregnant subjects and elemental concentrations of breast milk and infant formula.

As part of a longitudinal investigation into mobilization of lead from the maternal skeleton during pregnancy and lactation, we have determined the daily intake of selected elements (hereafter called micronutrients) for various subjects and compared these intakes with recommended and/or published intakes, especially those of the United States, through the U.S. National Health and Nutrition Examination Survey (NHANES). We also sought to ascertain whether there was any seasonal effect in the diets. Six-day duplicate diets were collected from 15 pregnant and 16 nonpregnant migrants to Australia, 6 pregnant Australian control subjects, and 8 children of nonpregnant migrants (6 to 11 years). Samples of breast milk and infant formula were also analyzed. Blended samples were analyzed by inductively coupled plasma mass spectrometry for the elements Ca, Cu, Fe, Mg, P, K, Na, Zn, Ba, Sr, and Pb. Daily intakes of micronutrients were only about half of the daily intake estimated for non-Hispanic white females and infants in the U.S. NHANES III. Estimates of daily intakes from breast milk were also considerably lower for the migrant and Australian infants compared with the values extracted from tables of food composition and dietary recall for non-Hispanic white infants in the U.S. NHANES III. For example, Ca was a factor of approximately 3 times lower, Fe approximately 50, and Zn approximately 4. We consider our estimates a reliable indication of the daily intakes for several reasons, including the collection of up to nine quarterly collections of 6-day duplicate diets and retention of subjects in a longitudinal prospective study. The low intakes of the essential elements such as Ca, Fe, and Zn in all these population groups are of potential concern from a public health viewpoint.

Limited seasonality effects on blood lead for a small cohort of female adults and children.

Many blood lead surveys, especially during the 1970s and 1980s have shown variations of up to 35% in blood lead concentration, with higher values in summer over winter. We have monitored 13 adult females and seven children for periods from 348 to 1337 days as non-pregnant controls in a longitudinal study of mobilization of lead from the maternal skeletal during pregnancy and lactation. Samples of blood, 6-day duplicate diet and environmental samples were analyzed by high-precision thermal ionization mass spectrometry for lead isotope ratios and lead concentrations. There was no statistically significant difference between seasons for blood lead concentrations and dietary intake although there were small differences in the isotopic composition for blood. One explanation for the lack of a seasonal effect in blood lead of our cohort may be the absence of climatic extremes in Sydney. The minimal effects from seasonality observed in this cohort make this an especially useful cohort within which to study effects that could be obscured by seasonal factors.

Recent advances in recognition of low-level methylmercury poisoning.

Clinically evident neurologic damage from methylmercury exposure was well described following poisoning episodes in Japan and Iraq several decades ago. Paresthesias have been considered to be an early effect; however, additional data raise questions about whether this is the most sensitive adverse effect among adults. Fetuses are considered the most sensitive subpopulation because of the vulnerability of the developing nervous system. Over the past 5 years questions have been raised about what is an appropriate level of exposure for sensitive groups. A recent evaluation by a committee for the US National Research Council found that 0.1 microg/kg body weight per day is a scientifically justified level of methylmercury exposure for maternal-fetal pairs. The conclusions of this report and other issues are discussed in the present review. Because of anthropogenic release of mercury into the environment, methylmercury exposure from fish consumption is a pathway that is of increasing concern.

Methylmercury: a new look at the risks.

In the US, exposure to methylmercury, a neurotoxin, occurs primarily through consumption of fish. Data from recent studies assessing the health impact of methylmercury exposure due to consumption of fish and other sources in the aquatic food web (shellfish, crustacea, and marine mammals) suggest adverse effects at levels previously considered safe. There is substantial variation in human methylmercury exposure based on differences in the frequency and amount of fish consumed and in the fish's mercury concentration. Although virtually all fish and other seafood contain at least trace amounts of methylmercury, large predatory fish species have the highest concentrations. Concerns have been expressed about mercury exposure levels in the US, particularly among sensitive populations, and discussions are underway about the standards used by various federal agencies to protect the public. In the 1997 Mercury Study Report to Congress, the US Environmental Protection Agency summarized the current state of knowledge on methylmercury's effects on the health of humans and wildlife; sources of mercury; and how mercury is distributed in the environment. This article summarizes some of the major findings in the Report to Congress and identifies issues of concern to the public health community.

Impact of diet on lead in blood and urine in female adults and relevance to mobilization of lead from bone stores.

We measured high precision lead isotope ratios and lead concentrations in blood, urine, and environmental samples to assess the significance of diet as a contributing factor to blood and urine lead levels in a cohort of 23 migrant women and 5 Australian-born women. We evaluated possible correlations between levels of dietary lead intake and changes observed in blood and urine lead levels and isotopic composition during pregnancy and postpartum. Mean blood lead concentrations for both groups were approximately 3 microg/dl. The concentration of lead in the diet was 5.8 +/- 3 microg Pb/kg [geometric mean (GM) 5.2] and mean daily dietary intake was 8.5 microg/kg/day (GM 7.4), with a range of 2-39 microg/kg/day. Analysis of 6-day duplicate dietary samples for individual subjects commonly showed major spikes in lead concentration and isotopic composition that were not reflected by associated changes in either blood lead concentration or isotopic composition. Changes in blood lead levels and isotopic composition observed during and after pregnancy could not be solely explained by dietary lead. These data are consistent with earlier conclusions that, in cases where levels of environmental lead exposure and dietary lead intake are low, skeletal contribution is the dominant contributor to blood lead, especially during pregnancy and postpartum.

Comparison of the rates of exchange of lead in the blood of newly born infants and their mothers with lead from their current environment.

Newly born infants (n = 15) were monitored for 6 months after birth or for longer periods to evaluate the changes in isotopic composition and lead concentration in infants as compared with that in women from the same population groups and to determine the clearance rates of lead from blood in the infants. These data represent the first published results for serial blood sampling in a relatively large cohort of newly born infants. Blood lead concentrations decrease from the cord to samples taken at 60 to 90 days and then increase by amounts varying from negligible to 166%. In spite of concern about individual susceptibility to lead pharmacokinetics, changes in isotopic ratio followed a smooth decrease over time for 9 of the 11 infants born to migrant parents, and the patterns of variation were quite reproducible. Data for 2 of 4 infants born to multigenerational Australian parents exhibited little change in isotopic ratio over time, and in the other two cases, the changes were attributed to diet. The rate of exchange (t1/2) for the migrant infants of lead in blood derived from the mother during pregnancy and the lead from the current environment was calculated by using a linear function and ranged from 65 to 131 (91+/-19, mean+/-SD) days. The half-lives for the exchange of skeletal and environmental lead for 7 of the 8 women before significant mobilization of lead from the maternal skeleton ranged from 50 to 66 (59+/-6) days. One explanation for the longer half-lives for infants as compared with the mothers may be the proportionally higher contribution of current environmental (Australian) lead in the infants at parturition. Exchanges of lead in infants are more complex than for the adults, reflecting inputs from sources such as maternal skeletal lead during breast feeding.

Predicting blood lead concentrations from lead in environmental media.

Policy statements providing health and environmental criteria for blood lead (PbB) often give recommendations on an acceptable distribution of PbB concentrations. Such statements may recommend distributions of PbB concentrations including an upper range (e.g., maximum and/or 90th percentile values) and central tendency (e.g., mean and/or 50th percentile) of the PbB distribution. Two major, and fundamentally dissimilar, methods to predict the distribution of PbB are currently in use: statistical analyses of epidemiologic data, and application of biokinetic models to environmental lead measurements to predict PbB. Although biokinetic models may include a parameter to predict contribution of lead from bone (PbBone), contemporary data based on chemical analyses of pediatric bone samples are rare. Dramatic decreases in environmental lead exposures over the past 15 years make questionable use of earlier data on PbBone concentrations to estimate a contribution of lead from bone; often used by physiologic modelers to predict PbB. X-ray fluorescent techniques estimating PbBone typically have an instrument-based quantitation limit that is too high for use with many young children. While these quantitation limits have improved during the late 1990s, PbBone estimates using an epidemiologic approach to describing these limits for general populations of children may generate values lower than the instrument's quantitation limit. Additional problems that occur if predicting PbB from environmental lead by biokinetic modeling include a) uncertainty regarding the fractional lead absorption by young children; b) questions of bioavailability of specific environmental sources of lead; and c) variability in fractional absorption values over a range of exposures. Additional sources of variability in lead exposures that affect predictions of PbB from models include differences in the prevalence of such child behaviors as intensity of hand-to-mouth activity and pica. In contrast with these sources of uncertainty and variability affecting physiologic modeling of PbB distributions, epidemiologic data reporting PbB values obtained by chemical analyses of blood samples avoid these problems but raise other issues about the validity of the representation of the subsample for the overall population of concern. State and local health department screening programs and/or medical evaluation of individual children provide PbB data that contribute to databases describing the impact of environmental sources on PbB. Overall, application of epidemiologic models involves fewer uncertainties and more readily reflects variability in PbB than does current state-of-the-art biokinetic modeling.

The contribution of lead-contaminated house dust and residential soil to children's blood lead levels. A pooled analysis of 12 epidemiologic studies.

In 1992, the U.S. Congress passed the Residential Lead-Based Paint Hazard Reduction Act, which requires the promulgation of health-based dust lead and soil lead standards for residential dwellings to prevent undue lead exposure in children. Unfortunately, the levels of lead in house dust and soil that are associated with elevated blood lead levels among U.S. children remain poorly defined. This pooled analysis was done to estimate the contributions of lead-contaminated house dust and soil to children's blood lead levels. The results of this pooled analysis, the most comprehensive existing epidemiologic analysis of childhood lead exposure, confirm that lead-contaminated house dust is the major source of lead exposure for children. These analyses further demonstrate that a strong relationship between interior dust lead loading and children's blood lead levels persists at dust lead levels considerably below the U.S. Department of Housing and Urban Development's current postabatement standards and the Environmental Protection Agency's guidance levels. Finally, these analyses demonstrate that a child's age, race, mouthing behaviors, and study-site specific factors influence the predicted blood lead level at a given level of exposure. These data can be used to estimate the potential health impact of alternative health-based lead standards for residential sources of lead exposure.

Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother.

We have obtained stable lead isotope and lead concentration data from a longitudinal study of mobilization of lead from the maternal skeleton during pregnancy and lactation and in which the newly born infants were monitored for 6 months postpartum to evaluate the effects of the local environment on lead body burden of the infant. Samples of maternal and infant blood, urine, and diet and especially breast milk were measured for 21 mothers and 24 infants. Blood lead concentrations were less than 5 microg/dl in all except one subject. The mean lead concentration in breast milk +/- standard deviation was 0.73 +/- 0.70 microg/kg. In seven subjects for whom serial breast milk sampling was possible, the lead concentration varied by factors of from 2 to 4, and for three subjects there was an increase at or after 90 days postpartum. For the first 60-90 days postpartum, the contribution from breast milk to blood lead in the infants varied from 36 to 80%. Multiple linear regression analyses indicated statistically significant relationships for some of the variables of isotope ratios and lead concentrations between breast milk, blood, urine, and diet for infants and mothers. For example, the analyses revealed that both a mother's breast milk 207Pb/206Pb and 206Pb/204Pb ratios and lead concentration provide information to predict her infant's blood 207Pb/206Pb and 206Pb/204Pb ratios. The major sources of lead in breast milk are from the maternal bone and diet. An evaluation of breast milk lead concentrations published over the last 15 years indicates that studies in which the ratio of lead concentrations in breast milk to lead concentrations in whole maternal blood (Multiple>100) were greater than 15 should be viewed with caution because of potential contamination during sampling and/or laboratory analyses. Selected studies also appear to show a linear relationship between breast milk and maternal whole blood, with the percentage of lead in breast milk compared with whole blood of <3% in subjects with blood lead levels ranging from 2 to 34 microgram/dl. The levels of lead in breast milk are thus similar to those in plasma. Breast-fed infants are only at risk if the mother is exposed to high concentrations of contaminants either from endogenous sources such as the skeleton or exogenous sources.

Blood lead-urine lead relationships in adults and children.

To determine the potential for using instead of blood as an indicator of lead exposure, especially in infants, lead concentrations and high-precision lead isotopic measurements have been compared in venous blood and "spot" urine (n > 260 from 182 different subjects) collected within the same 24-h period. Physiological conditions for the children and most of the adults were considered to be in a steady-state between body stores and lead in the environment. In the case of some adults, conditions were initially not steady-state because exposure conditions changed (for example, subjects moved to a country with lead of different isotopic composition.) There was a high correlation (r2 = ) between the blood and urine measurements of the isotope ratios but about 10% of measurements were outliers--the blood and urine measurements were further apart than was consistent with the measurement error that was generally obtained. The discrepancy was usually found to be associated with the urine measurement and was attributed to contamination during sampling. Weekly urine and monthly blood monitoring of an adult male over a 24-month period showed and excellent correlations, although the standard deviations were about an order of magnitude higher than the precision measured for replicate analyses of a single blood or urine sample. "Spot" urine analyses for two male subjects gave excellent agreement with 24-h urine samples. Standard deviations of the spot analyses were of similar order to those in the 24-month monitored subject. In cases where female adults from Eastern Europe migrated to Australia, there was generally a more rapid exchange of skeletal lead with Australian environmental lead in urine compared with blood. These data do not support a differential partitioning of endogenous lead into the plasma. At this stage, isotopic measurements of urine can be used as a proxy for isotopic measurements in blood. However, lead concentrations in blood and in urine are only weakly related. Concentrations of lead in urine cannot serve to predict concentrations of lead in blood, particularly at the lower range of exposures, for example, at blood concentrations less than 10 microgram/d1.

Blood levels of total and organic mercury in residents of the upper St. Lawrence River basin, Québec: association with age, gender, and fish consumption.

Increased consumption of lake fish was associated with higher blood mercury concentrations among 289 residents of Southwest Quebec living on the southern bank of the Upper St. Lawrence River System. This increase in blood mercury was reflected in the organic fraction and to a lesser extent with total blood mercury. Repeat analyses on a small subpopulation showed a correlation coefficient between time 1 and time 2 of approximately 0.7 for total mercury and for organic mercury. With one exception, blood total mercury concentrations were less than 5 ppb. Blood mercury concentrations were higher among men than women. One individual had much higher total mercury concentrations in blood (i.e., 70 ppb) which were attributed to fish consumption based on medical and dietary history. The values for these subjects are compared with other North American data on blood mercury levels.

Mobilization of lead from the skeleton during the postnatal period is larger than during pregnancy.

A cohort of 15 immigrant females to Australia and 7 native Australian controls were monitored on a monthly basis with high-precision lead isotopic methods during gestation and for 6 months after pregnancy to determine the extent of lead mobilization from the maternal skeleton. Quarterly environmental samples of house dust, drinking water, urban air, gasoline, and a 6-day duplicate diet were also measured. The geometric mean blood lead concentration for the immigrant females on arrival in Australia was 3.0 microg/dl (range: 1.9 to 20 microg/dl), and for the Australian controls was 3.1 gm/dl (range: 1.9 to 4.3 microg/dl). During gestation and after pregnancy, blood lead concentrations varied, with mean individual changes of -14% to 83%. For the immigrant subjects, the percentage change in blood lead concentration was significantly greater during the postpregnancy period than during the 2nd and 3rd trimesters (p < 0.001). Skeletal contribution to blood lead, based on the isotopic composition for the immigrant subjects, increased in an approximately linear manner during pregnancy. The mean increases for each individual during pregnancy varied from 26% to 99%. Skeletal lead contribution to blood lead was significantly greater (p < 0.001) during the postpregnancy period than during the 2nd and 3rd trimesters. The contribution of skeletal lead to blood lead during the postpregnancy period remained essentially constant at the increased level of lead mobilization, although the duration of breastfeeding varied from 1 week to more than 6 months. The increased contribution of skeletal lead to blood lead during the postpregnancy period is attributed to increased mobilization of lead from maternal skeletal stores during lactation. The increased contribution of skeletal lead both during pregnancy and in the postpregnancy period is consistent with increased bone resorption, and may be associated with an inadequate calcium intake observed in quarterly 6-day duplicate diets. Mobilization of skeletal lead stores represents a potentially important source of perinatal lead intake and accumulation in the developing fetus. Only two subjects consumed dietary supplements for calcium, and their mobilization of lead from the skeleton to the blood was the lowest of all the subjects. These two subjects' use of calcium supplements may have reduced mobilization of skeletal mineral stores to supply the calcium needs of pregnancy and lactation. Calcium supplementation may be an important means of limiting fetal exposure to lead.

Pregnancy increases mobilization of lead from maternal skeleton.

The question of the extent of lead mobilization from the maternal skeleton during pregnancy and lactation is one of the most outstanding problems of lead toxicity. We have undertaken a longitudinal cohort study in an urban environment of European female immigrants of child-bearing age (18 to 35 years) to Australia whose skeletal lead isotopic composition has been determined to be different from that in their current environment. The cohort was to consist of 100 immigrants anticipated to provide 20 pregnant subjects who would be compared with two groups of control subjects: a matched immigrant nonpregnant control group and second-generation Australian pregnant control subjects. Pregnant subjects also serve as their own controls for a comparison of changes during gestation with those before conception. High-precision lead isotopic compositions and lead concentrations are measured in maternal blood and urine prenatally, monthly during gestation, and postnatally for 6 months; they are also measured in infant blood and urine for 6 months; environmental measures are sampled quarterly for 6-day duplicate diet, house dust and water, and urban air and gasoline. Because of continuing public health concerns about lead exposure, interim findings from this cohort are being reported. To date there have been 13 conceptions in immigrant subjects, with 7 births, in addition to 3 conceptions in the Australian control group, with 2 births. PbBs have been generally low, with a geometric mean of 3.0 microg/dl, and have ranged from 1.9 to 20 microg/dl. Increases in PbB of approximately 20% during pregnancy have been detectable even in subjects with low blood lead levels. The skeletal contribution to blood lead level, based on isotopic measurements, has exhibited a mean increase (and standard deviation) of 31% +/- 19% with a range from 9% to 65%. Earlier studies that used lead concentrations only have suggested that blood lead levels increased only during the second half of pregnancy. This increase in blood lead levels has also been observed in the present study. However, in two subjects the increases in total blood lead were also detected in the first 2 months of pregnancy. Changes in isotopic composition and blood lead during gestation for Australian pregnant controls were negligible. The ratio of cord/maternal blood lead levels varied from 0.54 to 1.05, and the ratio for the isotopic composition was 0.993 to 1.002. Results of this study confirm that lead is mobilized from skeletal stores at an accelerated rate during pregnancy and is transferred to the fetus. These results also show that mobilization from long-term stores (i.e., bone) contributes significantly to blood lead levels during pregnancy. Furthermore, exposure of the fetus to lead during pregnancy has implications for interpretations of neurobehavioral disorders attributed to only postnatal exposure. Even after 800 days of residence in Australia, the contribution of European skeletal lead to blood lead in nonpregnant subjects can be on the order of 50%, but the current PbB may give no indication of the former high skeletal lead burden.

Dietary lead intakes for mother/child pairs and relevance to pharmacokinetic models.

Blood and environmental samples, including a quarterly 6-day duplicate diet, for nine mother/child pairs from Eastern Europe have been monitored for 12 to >24 months with high precision stable lead isotope analysis to evaluate the changes that occur when the subjects moved from one environment (Eastern Europe) to another with different stable lead isotopes (Australia). The children were between 6 and 11 years of age and the mothers were between 29 and 37 years of age. These data were compared with an Australian control mother/child pair, aged 31 and 6 years, respectively. A rationale for undertaking this study of mother/child pairs was to evaluate if there were differences in the patterns and clearance rates of lead from blood in children compared with their mothers. Blood lead concentrations ranged from 2.1 to 3.9 microg/dl in the children and between 1.8 and 4.5 microg/dl in the mothers, but the mean of differences between each mother and her child did not differ significantly from zero. Duplicate diets contained from 2.4 to 31.8 microg Pb/kg diet; the mean+/- standard deviation was 5.5 +/- 2.1 microg Pb/kg and total daily dietary intakes ranged from 1.6 to 21.3 microg/day. Mean daily dietary intakes relative to body weight showed that the intake for children was approximately double that for the mothers (0.218 vs. 0. 113 microg Pb/kg body weight/day). The correlations between blood lead concentration and mean daily dietary intake either relative to body weight or total dietary intake did not reach statistical significance (p>0.05). Estimation of the lead coming from skeletal (endogenous) sources relative to the contribution from environmental (exogenous) sources ranges from 8 to 70% for the mothers and 12 to 66% for the children. The difference between mothers and children is not statistically significant (p = 0.28). The children do not appear to achieve the Australian lead isotopic profile at a faster rate than their mothers. These data provide evidence that the absorption or uptake of lead from dietary sources is similar in adult females and children of the age in this study. In spite of lower bone lead and faster bone remodeling and recycling in children compared with adult females, we see no differences between the mothers and their children in overall contribution of tissue lead to blood lead. Results from this study suggest that fractional absorption of ingested lead by children 6-11 years of age is comparable with absorption patterns observed among adult females in the 29-37-year-old age range. Because pharmacokinetic models apply a 40-50% absorption even for 7-year-old children, further investigations on fractional absorption of ingested lead by young children are warranted. Further investigations are especially needed in younger children than those who were subjects in the current study, particularly children in the 1-3-year-old age range. In addition, the effect of nutritional status and patterns of food intake on children's lead absorption require investigation, particularly given the increased prevalence of marginal nutritional status among low-income populations that are at increased risk of elevated blood lead levels.

Stable lead isotope profiles in smelter and general urban communities: a comparison of environmental and blood measures.

High-precision lead isotope ratios and lead concentrations have been compared statistically and graphically in women of child-bearing age (n = 77) from two smelter communities and one general urban community to evaluate the relative contributions to blood lead of tissue lead stores and lead from the contemporaneous environment (soil, floor dust, indoor airborne dust, water, food). Blood lead (PbB) contents were generally low (e.g. <10 µg dL(-1)). Statistically significant isotopic differences in blood and environmental samples were observed between the three cities although isotopic differences in blood for individual subjects living in close proximity (∼200 m radius) was as large as the differences within a city. No single environmental measure dominated the biological isotope profile and in many cases the low levels of blood lead meant that their isotopic profiles could be easily perturbed by relatively small changes of environmental exposure. Apportioning of sources using lead isotopes is possibly not feasible, nor cost effective, when blood lead levels are <5 µg dL(-1). Interpretations based on statistical analyses of city-wide data do not give the same conclusions as when the houses are considered individually. Aggregating data from multiple subjects in a study such as this obscures potentially useful information. Most of the measures employed in this study, and many other similar studies, are markers of only short-to-medium integration of lead exposure. Serial sampling of blood and longer sampling times, especially for household variables, should provide more meaningful information.

Holistic risk assessment: an emerging process for environmental decisions.

A holistic risk assessment (HRA) strategy is proposed as an alternative, inclusive paradigm which builds upon the traditional risk assessment process described by the National Academy of Sciences. This proposed process expands beyond the traditional process in that it: (i) includes parallel and integrated assessments for ecological risk and human health risks; (ii) recognizes the presence of competing risks that may arise from implementation of risk management decisions; (iii) is an iterative and nonsequential process that highlights the importance of risk characterization and the need for comparisons; (iv) has focus on presenting a series of risk choices that take into consideration parameters specific to exposed populations and ecosystems; and (v) involves communication as the first step between risk assessors and risk managers, with subsequent communication of the results of the assessment to clients and the public. This HRA strategy is illustrated by a case study on methyl mercury. Specific research is proposed for future improvements in this area.