Mercury and methylmercury exposure in the New Jersey pregnant population.

Methylmercury is a known fetal developmental neurotoxicant. The only significant source of fetal exposure is maternal fish consumption; however, few recent data on exposure of the pregnant population are available. The authors undertook a study of methylmercury exposure in the New Jersey pregnant population to investigate the distribution of exposure and to identify predictors of elevated exposure. Mainly first-trimester pregnant women were recruited through six New Jersey obstetric practices. Hair and blood samples were analyzed for total mercury, and a subset was analyzed for methylmercury. A questionnaire on demographics, life style, and fish-consumption practices was also administered. Although 85-90% of the pregnant population had hair mercury levels that were less than 1.0 microg/gm, 1-2% had levels in a range of possible concern for adverse developmental effects (> 4.0 microg/gm). Regression analysis suggested that blacks and individuals with some college education experienced lower exposures to methylmercury.

How useful is linear regression analysis in detecting the existence of dose-response relationships in large-scale epidemiologic studies when only a fraction of the population is sensitive? The case of methylmercury.

The existence of a dose response in epidemiologic studies is generally determined from the linear regression slope after controlling for covariates. This approach assumes the entire population is equally sensitive to the toxicant and that response is a function only of dose and a random error function. However, sensitive subpopulations have been identified for a variety of toxicants possibly including methylmercury (MeHg). The study of MeHg exposure in the Seychelles Islands has failed to find significant effects (dose-response slope not significantly different from zero) while other studies have found such effects. Using data on the error function in developmental test scores and MeHg exposure distributions from that study, and assuming plausible dose-response relationships for sensitive subpopulations, we conducted Monte-Carlo simulations of the power of linear regression analysis to detect a dose-response relationship from the total sample (n=700), and to compare dose-response slopes in the total and sensitive populations. Linear regression did not reliably detect a dose-response relationship for most scenarios when sensitives were 5% of the total and for some scenarios when sensitives were 10% of the total. We also found that the dose-response slope for the total population underestimated the sensitive dose-response slope in all cases by about an order of magnitude. These findings may have important implications for detection and quantification of dose-response relationships from epidemiologic studies.

Reduction in residential chromium following site remediation.

The purpose of this study was to determine the influence of chromate production waste site remediation on residential Cr concentrations in house dust. Twenty-three homes in Jersey City, NJ, were identified as having had high (> 500 micrograms/gm, median 739 micrograms/gm), medium (100-400 micrograms/gm, median 245 micrograms/gm), or low (< 100 micrograms/gm, median 48 micrograms/gm) Cr in house dust during a study conducted in 1992-1993 prior to site remediation. House dust samples were collected on four visits from each home between November 1996 and February 1998, extracted with HNO3, and analyzed for Cr with an inductively coupled plasma-mass spectrometer. Homes that had low Cr concentrations in 1992-1993 continued to have low Cr concentrations (median 1 microgram/g). In contrast, substantial declines in Cr concentrations were found in the house dust collected from homes located near the remediated waste sites: previously high-level homes had a median of 50 micrograms/g and mid-level homes had a median of 34 micrograms/g. Site remediation had a beneficial effect on household loadings of Cr, since no differences in post-remediation house dust Cr concentrations were found among the three groups.

The association of chromium in household dust with urinary chromium in residences adjacent to chromate production waste sites.

Several previous studies of exposure to chromium waste in New Jersey have shown that Cr levels are elevated in household dust in homes adjacent to waste sites and that Cr levels in the urine of residents near sites are also elevated compared to control populations. It has not been possible until now, however, to examine these external and internal measures of exposure together in a large population to determine whether the external exposure is predictive of the internal exposure. We investigated the relationship between various adjusted and unadjusted measures of spot urine Cr concentration and household dust Cr from residents and residences adjacent to known Cr waste sites. Statistically significant bivariate relationships were found between log-transformed urine Cr concentration and Cr dust concentration (micrograms of Cr per gram of dust) but not Cr dust loading (nanogram Cr per square centimeter). Log-transformed urine concentration was used as the dependent variable in multiple regression analysis of the total population (n = 329), the population [less than/equal to] 10 years old (n = 67), and the population >10 years old (n = 262), with Cr dust concentration as a mandatory independent variable. Other potential direct influences on urine Cr were investigated as potential confounders of this relationship. In the final models for the entire population and those [less than/equal to] 10 years old, but not for those >10 years old, Cr dust concentration remained significant. This suggests that exposure of young children to Cr in household dust accounts for much of the relationship in the entire population.

Estimation of the interindividual variability in the one-compartment pharmacokinetic model for methylmercury: implications for the derivation of a reference dose.

A critical step in the U.S. EPA's derivation of an Reference Dose (RfD) for methylmercury is conversion of the maternal hair Hg concentration of 11 ppm to average daily intake using the one-compartment pharmacokinetic model. A default uncertainty factor (UF) adjustment of 3 for interindividual variability was then applied to this conversion. A probabilistic (Monte Carlo) analysis is presented estimating the interindividual variability inherent in this dose conversion for women 18-40 years old based on data in the scientific literature. The dose of 1.1 micrograms/kg/day, calculated by the U.S. EPA to correspond to 11 ppm Hg in hair, is estimated in this analysis to be larger than 94-99% of corresponding doses. The application of a UF of 3 to this U.S. EPA value gives a dose which is estimated to be larger than 28-73% of corresponding doses. This analysis suggests that if the dose conversion in the RfD is intended to be inclusive of 95-99% of women 18-40, the daily intake should be set at 0.1-0.3 microgram/kg/day. The RfD of 0.03-0.1 microgram/kg/day, derived from this dose by the U.S. EPA's application of an additional UF of 3 for additional toxicologic concerns, is somewhat smaller than the current RfD of 0.1 microgram/kg/day.

Exposure to chromium dust from homes in a Chromium Surveillance Project.

Investigators used a Lioy-Weisel-Wainman sampler to analyze the chromium content in house-dust samples obtained from households near chromium waste sites in Hudson County, New Jersey. Chromium concentrations in dust (microg/g)-indicative of non-background source contributions-were significantly higher in Jersey City homes than in control homes outside of Hudson County (228 and 111 microg/g, respectively; p < .001). Chromium dust loadings on surfaces (ng/cm2), representing the amount of chromium available for contact and a direct measure of exposure potential, were also higher in Jersey City homes than in control homes (31 ng/cm2 and 14 ng/cm2, respectively; p = .008). Near some of the sites, investigators found elevated chromium dust loads more frequently in homes occupied by at least one household member who had elevated urine chromium, as determined in a separate screening project, than in homes occupied by members whose urine chromium was not elevated. Individuals with elevated urine chromium levels were found less frequently in homes in which good housekeeping practices were evident than in homes absent such practices.

Estimation of fish consumption and methylmercury intake in the New Jersey population.

Despite scientific attention to the toxicology of methylmercury (MeHg), little is known about population-based exposure to this compound. In this study, fish consumption and MeHg intake were estimated based on a seven-day recall survey of fish consumption among 1000 randomly selected New Jersey residents. Survey data were reported on a per-meal basis, and the fish species/dishes consumed at each meal were identified. Portion sizes for each meal were reported or estimated. To correct a possible bias due to underrepresentation of infrequent consumers, several schemes for weighting fish consumption data were investigated. MeHg concentration for most fish species was estimated from the National Marine Fisheries Service database or from recent United States Food and Drug Administration data. Commercial fish accounted for about 95% of all consumption. Mean fish consumption is estimated for all New Jersey adult consumers at 50.2 g/day (90th percentile = 107.4 g/day) and for women 18-40 years old (childbearing age) at 41.0 g/day (90th percentile = 88.1 g/day). Mean MeHg intake is estimated for all New Jersey adult consumers at 7.5 micrograms/day (90th percentile = 1.79 micrograms/day) and for women 18-40 at 6.3 micrograms/day (90th percentile = 14.8 micrograms/day). When MeHg concentrations are adjusted to account for the possible overestimation of current concentrations by the 20-year-old National Marine Fisheries Service database, it is estimated that MeHg intakes may be about 70-80% of unadjusted estimates. Based on these analyses, it is estimated that 21-30% of New Jersey women 18-40 and 5-8% of all New Jersey adults exceed their respective U.S. Environmental Protection Agency Reference Doses for MeHg. Because of uncertainty associated with the Reference Doses, exceeding the U.S. Environmental Protection Agency guidelines does not necessarily correspond to adverse effects on consumers or their fetuses.

Derivation of a target concentration of Pb in soil based on elevation of adult blood pressure.

The increase in systolic blood pressure in males appears to be the most sensitive adult endpoint appropriate for deriving a health risk-based target level of lead (Pb) in soil. Because the response of blood pressure to blood Pb concentration (PbB) has no apparent threshold, traditional approaches based on the application of a Reference Dose (RfD) are not applicable. An alternative approach is presented based on a model which predicts the population shift in systolic blood pressure from ingestion of Pb contaminated soil as a simultaneous function of exposure to Pb in soil, the baseline distribution of blood Pb concentration in the population and baseline distribution of systolic pressure in the population. This model is analyzed using Monte Carlo analysis to predict the population distribution of systolic pressure resulting from Pb exposure. Based on this analysis, it is predicted that for adult males 18-65 years old, exposure to 1000 ppm Pb in soil will result in an increase of approximately 1 mm Hg systolic pressure, an increase in the incidence of systolic hypertension (i.e., systolic pressure > 140 mm Hg) of approximately 1% and an increase in PbB of 1-3 micrograms/dl. Based on the proposition that these adverse effects can be considered de minimis, 1000 ppm Pb in soil is proposed as a target soil concentration for adult exposure. Available data do not appear to be adequate to predict the newborn PbB level which would result from exposure to this soil level during pregnancy.

The effect of remediation of chromium waste sites on chromium levels in urine of children living in the surrounding neighborhood.

Exposure to chromium was assessed for 40 children living near chromium waste sites. Sampling was conducted in one Jersey City, New Jersey neighborhood during the summer and fall of 1991. Household dust samples from residences and urine samples from children living near chromium waste sites were collected and analyzed for chromium. During the summer and fall visits when the samples were collected, the children were also interviewed about lifestyle/activity patterns. Comparisons were made with similar samples collected from children and homes in other areas of New Jersey outside of Hudson County with no known chromium waste sites. Household dust masses and chromium loadings and concentrations in the dust showed a significant decline in this Hudson County neighborhood since the area was first sampled in 1990. Interim remediation of neighborhood sites and an active community education program in the interval between the first and second year of sampling may have contributed to the reduction in dust masses and chromium levels in dust. Children's urine chromium concentrations were consistent across the two sampling periods despite reported changes in activity patterns. Chromium concentrations in urine were found to be age-dependent and related to home location. In this sample of Jersey City children less than six years old, time spent playing outdoors was a weak secondary contributor to urine chromium levels.

Derivation of a target level of lead in soil at residential sites corresponding to a de minimis contribution to blood lead concentration.

Inability to define either a clear toxicologic threshold or a stochastic all-or-nothing (cancer-type) response model for the noncarcinogenic effects of lead (Pb) in young children has posed difficulties for derivation of risk-based target levels of Pb in residential soil. Approaches based on empirical relationships between Pb levels in blood (PbB) and Pb in soil suffer from inability to specify the numerous variables which mediate between these two quantities. Approaches based on achieving a toxicologically de minimis target PbB level (e.g., 10 micrograms/dl) are subject to large uncertainty in estimating the distribution of existing PbB levels in a specific exposed population and in estimating the relative contribution from nonsoil sources of Pb. The multisource contribution to the distribution of PbB makes this approach unsuited for determination of a target Pb level in a single medium. An alternative approach is presented based on achieving a de minimis contribution to PbB (delta PbB) from soil. Contributions to Pb exposure from outdoor soil and indoor soil-derived dust (ISDD) are modeled and appropriate values are suggested for input parameters. This analysis predicts that chronic exposure of young children to 200 micrograms Pb/g (ppm) in residential soil will result in a delta PbB of 2 micrograms Pb/dl blood. This concentration of Pb in soil may provide an appropriate target level for residential soil when other significant sources of Pb exposure are present. In other cases, this approach can be used to predict a soil concentration of Pb corresponding to an appropriate non-de minimis delta PbB.

Risk assessment of the allergic dermatitis potential of environmental exposure to hexavalent chromium.

Although hexavalent chromium, Cr(VI), is a potent sensitizer and inducer of allergic contact dermatitis and is found in many common materials, no standard or guideline currently exists for protection against these effects in environmental exposure. There appears to be a generalized allergenic potential among the various compounds of Cr(VI). Estimates of the prevalence of Cr sensitivity in the population are uncertain, but range from about 2% of the total population in Finland to as high as 20% in U.S. populations with a dermatitis. Based on the thresholds reported for nine separate patch-test studies and statistical analysis of the aggregate dose-response relationship from 72 separate observations from these studies and on studies of allergic responses to bleaches and detergents, the effective threshold for elicitation of allergic contact dermatitis in sensitized populations is about 10 ppm (mg/L) Cr(VI) (as chromium) in solution. Based on evaluation of the literature on cement dermatitis, the threshold concentration of extractable Cr(VI) in solid material may be as low as 10 ppm (microgram/g). For ingestion of Cr(VI), the lowest observed effect level (LOEL) dose for elicitation is 0.26 microgram/kg. In calculating the threshold concentration of Cr(VI) in soil for elicitation of contact dermatitis, extractability must be taken into account.

Monte Carlo analysis of the U.S. EPA model of human exposure to cadmium in sewage sludge through consumption of garden crops.

The derivation of the recently promulgated U.S. EPA regulations for land application of sewage sludge considered a model of human exposure to cadmium (Cd) from consumption of garden crops grown on sludge-amended soil. The EPA approach to the calculation of the maximum acceptable loading rate of Cd to soil from this pathway employs single point estimates for each input variable. It also considers Cd uptake slopes for crops grown in sludge-amended soils with pH from 4.4-8.4. The complexity and variability inherent in this pathway argue against obtaining a realistic assessment of this pathway with point estimates of input parameters. Furthermore, the use of uptake slopes from alkaline soils is likely to lead to underestimating Cd uptake from acidic soils prevalent in the eastern and southern United States. A re-analysis of this pathway is presented employing Monte Carlo probabilistic analysis of the exposure variables with Cd uptake slopes restricted to soils with pH < or = 6.5. Despite uncertainties in the derivation of some probabilistic inputs, this approach appears to present a more realistic assessment of this pathway.

Re-evaluation of the reference dose for methylmercury and assessment of current exposure levels.

Methylmercury (Me-Hg) is widely distributed through freshwater and saltwater food chains and human consumption of fish and shellfish has lead to widespread exposure. Both the U.S. EPA Reference Dose (0.3 micrograms/kg/day) and the FAO/WHO Permissible Tolerable Weekly Intake (3.3 micrograms/kg/week) are currently based on the prevention of paraesthesia in adult and older children. However, Me-Hg exposure in utero is known to result in a range of developmental neurologic effects including clinical CNS symptoms and delayed onset of walking. Based on a critical review of developmental toxicity data from human and animal studies, it is concluded that current guidelines for the prevention of paraesthesia are not adequate to address developmental effects. A dose of 0.07 micrograms/kg/day is suggested as the best estimate of a potential reference dose for developmental effects. Data on nationwide fish consumption rates and Me-Hg levels in fish/seafood weighted by proportion of the catch intended for human consumption are analyzed in a Monte Carlo simulation to derive a probability distribution of background Me-Hg exposure. While various uncertainties in the toxicologic and exposure data limit the precision with which health risk can be estimated, this analysis suggests that at current levels of Me-Hg exposure, a significant fraction of women of childbearing age have exposures above this suggested reference dose.

Residential exposure to chromium waste--urine biological monitoring in conjunction with environmental exposure monitoring.

To determine whether a population living on or adjacent to four sites of chromate production waste was measurably exposed to environmental chromium, spot samples of urine were collected along with wipe samples of household dust and lifestyle/activity interview data. Findings were compared to those from a control population in two communities with no significant chromium use or waste sites. Urine samples were collected and analyzed, employing measures to minimize background chromium contamination. The average Cr mass in dust was 3.7 times that in control houses. The mean creatinine-corrected urine Cr (Cr/c) level of the exposed subgroup residing in households in the 75th percentile of Cr mass in wipe samples was significantly greater than that of the control population. This subgroup was primarily located at a single exposure location. Using lifestyle/activity data, significantly elevated Cr/c urine levels were identified in other exposed subgroups defined by employment location and by outside play time. These data show an association between elevated exposure to chromium in household dust and elevated urine levels of chromium, consistent with residential exposure to chromate production waste. These data also suggest an association between chromium exposure and activities outside the home which are consistent with exposure to chromate production waste.

Microenvironmental analysis of residential exposure to chromium-laden wastes in and around New Jersey homes.

The purpose of this study was to identify the significant microenvironments that can lead to chromium exposure in Hudson County, New Jersey residential settings near or on soil contaminated with chromium waste. Measurements were made in indoor air, outdoor air, and house dust. Surface dust was found to be the best index of potential Cr exposure. The values of Cr in Hudson County household dust ranged from 3.25-320 ng/cm2 in wipe samples and 1.0-12 ng/cm2 in vacuum samples. Elevated Cr in household dust was found to be related to residential locations near large chromium waste sites, household cleaning habits, and house renovation activities. Outdoor Cr air levels were similar to those obtained in other urban areas at these seasons of the year, approximately 5-7 ng/m3. Comparisons with measurements of the Cr levels in urine found that the elevated Cr in dust was associated with elevated excretion of Cr. Site-specific Cr differences in household dust suggest different sources and routes of exposure. Within the total group of homes in the present study, Cr in household dust was the major influence on household exposure.