Evaluation and improvement of QSAR predictions of skin sensitization for pesticides.

In vivo skin sensitization assays have to be provided by applicants to the competent authorities in the European Union for the approval of active substances (AS) in pesticides. This study aimed to test the practicability of in silico predictions for AS by freely available (Q)SAR tools to evaluate their use as a time- and cost-effective alternative to animal testing in the context of the 3R concept. Predictions of skin sensitization for 48 selected sensitizing and non-sensitizing AS by the software programs CAESAR, Toxtree, OECD (Q)SAR Toolbox, CASE Ultra, Leadscope and SciQSAR were collected and compared. Different data evaluation methodologies (score definition, mean, weighted mean, threshold score definition) were applied to optimize the predictions. The calculation methods were internally cross-validated and further validated with an additional validation set of 80 AS. Although the presented calculation methodologies are not suitable as a stand-alone method, this study has shown weaknesses and strengths of some prominent (Q)SAR programs and diverse combinatorial options in the prediction of skin sensitization by pesticidal AS. The present study will help to foster discussions on in silico alternatives to animal testing in the pesticide area.

Biometrical evaluation of the performance of the revised OECD Test Guideline 402 for assessing acute dermal toxicity.

A comprehensive biometrical assessment was conducted to compare the performance of multiple test designs for acute dermal systemic toxicity to support the animal welfare update to the original OECD Test Guideline (TG) 402 for acute dermal toxicity. The test designs evaluated included: (1) two, three, or five animals per dose group (2) evident toxicity or lethality endpoints and (3) absence or presence of a one-animal sighting study. The revision of TG 402 respected the 3R principles (replace, reduce, refine) of animal testing. The results demonstrate that the TG 402 test design can be optimised with reduced animal numbers per test group, such that a scenario of two animals per group following a sighting study at a starting dose of 200 mg/kg bw (unless further information is available to better define the starting dose) would provide a classification which in most cases is conservative, without compromising both the statistical ability of the study to assess dermal toxicity, or the relevant classification outcome.

The importance of protein binding for the in vitro-in vivo extrapolation (IVIVE)-example of ibuprofen, a highly protein-bound substance.

A physiologically based human kinetic model (PBHKM) was used to predict the in vivo ibuprofen dose leading to the same concentration-time profile as measured in cultured human hepatic cells (Truisi et al. in Toxicol Lett 233(2):172-186, 2015). We parameterized the PBHKM with data from an in vivo study. Tissue partition coefficients were calculated by an algorithm and also derived from the experimental in vitro data for the liver. The predicted concentration-time profile in plasma was in excellent agreement with human experimental data when the liver partition coefficient was calculated by the algorithm (3.01) demonstrating values in line with findings obtained from human postmortem tissues. The results were less adequate when the liver partition coefficient was based on the experimental in vitro data (11.1). The in vivo doses necessary to reach the in vitro concentrations in the liver cells were 3610 mg using the best fitting model with a liver partition coefficient of 3.01 compared to 2840 mg with the in vitro liver partition coefficient of 11.1. We found that this difference is possibly attributable to the difference between protein binding in vivo (99.9 %) and in vitro (nearly zero) as the partition coefficient is highly dependent on protein binding. Hence, the fraction freely diffusible in the liver tissue is several times higher in vitro than in vivo. In consequence, when extrapolating from in vitro to in vivo liver toxicity, it is important to consider non-intended in vitro/in vivo differences in the tissue concentration which may occur due to a low protein content of the medium.

Caffeine intake in pregnancy: Relationship between internal intake and effect on birth weight.

We used a physiologically based kinetic model to simulate caffeine blood concentration-time profiles in non-pregnant and pregnant women. The model predicted concentration-time profile was in good accordance with experimental values. With 200 mg, the safe dose per occasion in non-pregnant women, AUC and peak concentration in pregnant women were nearly twice that of non-pregnant women. In order to derive a safe dose for the pregnant women we estimated the dose in the pregnant women model taken at once which would not exceed AUC and peak concentration in the non-pregnant women of 200 mg as single dose. The resulting dose is 100 mg caffeine per occasion which we recommend as safe. The caffeine dose of 200 mg per day is declared as safe for pregnant women with respect to the foetus by EFSA based on results on reduced birth weight in epidemiological studies. We modelled AUC and peak concentration for different caffeine doses to investigate the relationship between internal caffeine exposure and risk measures of reduced birth weight from epidemiological studies. The graphical analysis revealed that the reduction in birth weight was related to AUC and peak concentration up to a dose of 250 mg caffeine.

In vitro - in vivo correlation of gene expression alterations induced by liver carcinogens.

Although cultivated hepatocytes are widely used in the studies of drug metabolism, their application in toxicogenomics is considered as problematic, because previous studies have reported only little overlap between chemically induced gene expression alterations in liver in vivo and in cultivated hepatocytes. Here, we identified 22 genes that were altered in livers of rats after oral administration of the liver carcinogens aflatoxin B1 (AB1), 2-nitrofluorene (2-NF), methapyrilene (MP) or piperonyl-butoxide (PBO). The functions of the 22 genes have been classified into two groups. Genes related to stress response, DNA repair or metabolism and genes associated with cell proliferation, respectively. Next, rat hepatocyte sandwich cultures were exposed to AB1, 2-NF, MP or PBO for 24h and expression of the above mentioned genes was determined by RT-qPCR. Significant correlations between the degree of gene expression alterations in vivo and in vitro were obtained for the stress, DNA repair and metabolism associated genes at concentrations covering a range from cytotoxic concentrations to non-toxic/in vivo relevant concentrations. In contrast to the stress associated genes, no significant in vivo/in vitro correlation was obtained for the genes associated with cell proliferation. To understand the reason of this discrepancy, we compared replacement proliferation in vivo and in vitro. While hepatocytes in vivo, killed after administration of hepatotoxic compounds, are rapidly replaced by proliferating surviving cells, in vitro no replacement proliferation as evidenced by BrdU incorporation was observed after washing out hepatotoxic concentrations of MP. In conclusion, there is a good correlation between gene expression alterations induced by liver carcinogens in vivo and in cultivated hepatocytes. However, it should be considered that cultivated primary hepatocytes do not show replacement proliferation explaining the in vivo/in vitro discrepancy concerning proliferation associated genes.

The contribution of dermal exposure to the internal exposure of bisphenol A in man.

New findings on Bisphenol A (BPA) contents in thermal printing papers, and receipts, in g/kg concentrations and on its dermal uptake (up to 60%) prompted us to assess the risk arising from dermal exposure. Using physiologically based toxicokinetic modelling, we simulated concentrations in blood, in liver and kidney, the target organs exhibiting the lowest no observed adverse effect levels (NOAEL). By comparing organ concentrations at the dose level of the NOAEL divided by a safety factor of 100 (liver: 50µg/kg/day; kidney: 500µg/kg/day), with concentrations arising from the dermal dose of 0.97µg/kg/day (worst case assumption by Biedermann et al., 2010) this dermal exposure can be assumed safe. Additionally, based on the model simulations the high blood concentrations, reported earlier in the literature, are highly improbable because the related exposure levels are orders of magnitude higher than the currently estimated aggregate exposure levels.

Children's blood lead and standardized test performance response as indicators of neurotoxicity in metropolitan New Orleans elementary schools.

This study analyzes pre-Katrina variation in aggregate student performance and children's blood lead (BPb) in 117 elementary school districts in metropolitan New Orleans. Fourth grade student achievement on Louisiana Educational Assessment Program (LEAP) tests were analyzed as a function of BPb for children 1-6 years old within school districts, controlling for student-teacher ratios, percent of students eligible for a free or discounted lunch, and school racial demography. Measures of performance across subject areas (English Language Arts, Science, Mathematics, and Social Studies) include school Achievement Test Scores (ATS) and indices of agreement and variation in student achievement. ATS are measured on a 5-point scale, corresponding to achievement categories of advanced=5 to unsatisfactory=1. Regression results show that median BPb (microg/dL) and percent of children with BPb > or =10 microg/dL are significantly associated with reductions in test scores across all subjects and depress variation in student performance across achievement categories. These data suggest that assisting children with improved school performance requires alleviation of pre-school Pb exposure and its associated neurotoxic damage. Cost-benefit calculations suggest that it is more cost effective to pay for onetime primary prevention instead of paying continuous expenses focused on reversing neurotoxic damage.

Collateral benefits and hidden hazards of soil arsenic during abatement assessment of residential lead hazards.

Abatement of soil-lead hazards may also reduce human exposure to other soil toxins, thereby achieving significant collateral benefits that are not accounted for today. This proposition was tested with the specific case of soil-arsenic, where 1726 residential soil samples were collected and analyzed for lead and arsenic. The study found that these two toxins coexisted in most samples, but their concentrations were weakly correlated, reflecting the differing sources for each toxin. Collateral benefits of 9% would be achieved during abatement of the lead-contaminated soils having elevated arsenic concentrations. However, a hidden hazard of 16% was observed by overlooking elevated arsenic concentrations in soils having lead concentrations not requiring abatement. This study recommends that soil samples collected under HUD programs should be collected from areas of lead and arsenic deposition and tested for arsenic as well as lead, and that soil abatement decisions consider soil-arsenic as well as soil-lead guidelines.

The influence of folic acid depletion on the Nucleotide Excision Repair capacity of human dermal fibroblasts measured by a modified Host Cell Reactivation Assay.

Animal and human studies have shown that low levels of folic acid are associated with an impaired DNA Repair Capacity (DRC) and an increased cancer risk. However, the molecular evidence that folic acid enhances the DRC of cultured human cells is still limited because of a paucity of in vitro studies. We investigated the effect of folic acid depletion in vitro on the DRC of human dermal fibroblasts derived from 17 donors of different ages. To assess the cellular Nucleotide Excision DRC, we used a modified Host Cell-Reactivation Assay (HCRA), adapted to the Fluorescence Activated Cell Sorting (FACS)-technology, which is highly sensitive in comparison to luminometer-technology and allows single cell based analysis. We used DsRed as a reporter (irradiated with UVC light) and pEGFP to control the performance of the transformations. Folic acid had a statistically significant effect on the DRC in all of the 17 donors, however, the levels varied considerably between individuals (2.0-19.6%). When the effect of folic acid substituted on the DRC was compared to donor age, we observed that there was less DNA repair in old donors compared to the younger donors, although this was only significant at lower levels.

Natural and anthropogenic processes that concentrate Mn in rural and urban environments of the lower Mississippi River delta.

This study evaluated natural processes and projected methylcyclopentadienyl manganese tricarbonyl fuel additives as sources of Mn accumulation in the environment. Data sets include fresh alluvium and sediments from the lower Mississippi River Delta and a soil metal survey of metropolitan New Orleans. The (1) railroad Mn, (2) industrial Mn, and (3) dynamic aquifer-stream transfer of Mn hypotheses were tested with the Mississippi River Delta data. Friction between Mn-rich steel wheels and rails contributes Mn (P = 0.017) to the environment, supporting (1). Sediment loads of Mn were similar (P = 0.77) upstream and downstream from the Louisiana industrial corridor, not supporting (2). The median Mn on the alluvium surface (59 mg/kg), in the aquifer (159 mg/kg), and in the riverbank aquifer discharge zone (513 mg/kg) support (3) as a mechanism for Mn enrichment of clay. The New Orleans soil metal survey data set shows a rural to urban increase of fourfold for Mn and three orders of magnitude for Pb. At 1999 U.S. highway fuel use, 8.3 mg of Mn per L would yield 5000 metric tons of Mn annually. If 13% of Mn were emitted, 650 tons of Mn would become aerosols annually, while 87% or 4350 tons would remain in engines. The 1999 toxic release inventory for Mn shows 370 tons as total emissions compared to the potential of 390 and 260 tons from vehicles, respectively, in urban and rural areas. A precautionary lesson from the use of Pb as a fuel additive is that the use of Mn as a fuel additive would be associated with an increased risk for neonates exceeding the estimated total tolerable daily intake of 2.1-16.5 micrograms Mn (especially in urban inner city environments) because neonates lack fully functional hepatic clearance for Mn.

Multiple metal contamination from house paints: consequences of power sanding and paint scraping in New Orleans.

Power sanding exterior paint is a common practice during repainting of old houses in New Orleans, Louisiana, that triggers lead poisoning and releases more than Pb. In this study we quantified the Pb, zinc, cadmium, manganese, nickel, copper, cobalt, chromium, and vanadium in exterior paint samples collected from New Orleans homes (n = 31). We used interior dust wipes to compare two exterior house-painting projects. House 1 was measured in response to the plight of a family after a paint contractor power sanded all exterior paint from the weatherboards. The Pb content (approximately 130,000 microg Pb/g) was first realized when the family pet died; the children were hospitalized, the family was displaced, and cleanup costs were high. To determine the quantity of dust generated by power sanding and the benefits of reducing Pb-contaminated dust, we tested a case study house (house 2) for Pb (approximately 90,000 microg/g) before the project was started; the house was then dry scraped and the paint chips were collected. Although the hazards of Pb-based paints are well known, there are other problems as well, because other toxic metals exist in old paints. If house 2 had been power sanded to bare wood like house 1, the repainting project would have released as dust about 7.4 kg Pb, 3.5 kg Zn, 9.7 g Cd, 14.8 g Cu, 8.8 g Mn, 1.5 g Ni, 5.4 g Co, 2.4 g Cr, and 0.3 g V. The total tolerable daily intake (TTDI) for a child under 6 years of age is 6 microg Pb from all sources. Converting 7.4 kg Pb to this scale is vexing--more than 1 billion (10(9)) times the TTDI. Also for perspective, the one-time release of 7.4 x 10(9) microg of Pb dust from sanding compares to 50 x 10(9) microg of Pb dust emitted annually per 0.1 mile (0.16 km) from street traffic during the peak use of leaded gasoline. In this paper, we broaden the discussion to include an array of metals in paint and underscore the need and possibilities for curtailing the release of metal dust.

PAH and metal mixtures in New Orleans soils and sediments.

The purpose of this study is to determine the degree of PAH contamination and the association of PAHs with inorganic substances in soils and sediments of New Orleans. Bonnet Carré Spillway (BCS) (n = 5) provides modern baseline data, while urban soil samples (CTY) (n = 27) and sediment samples from Bayou St. John (BSJ) (n = 11) provide experimental data for New Orleans. Soil samples were collected from the top 2.5 cm of the surface, air-dried, and sieved (2 mm). Sediments samples were collected with a Wildco-Ekman bottom dredge, air-dried and finely ground. Accelerated solvent extraction (ASE) was used to release PAHs from the samples and analysis was conducted with gas chromatography-mass spectrometry (GC-MS). Metals were extracted using a 5:1 ratio of 1 mol/L nitric acid (room temperature) for soil and sediment samples, shaken for 2 h, centrifuged (1000 x g for 15 min) and filtered. Metal analysis was done by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Mann-Whitney tests show PAH differences (P < 0.001). Ranking of total PAHs is, BSJ sediments (10.3 mg/kg) > CTY soils (3.7 mg/kg) > BCS alluvium (0.28 mg/kg). The sum of the metals are similar for BSJ sediments (698 mg/kg) and CTY soils (679 mg/kg) and significantly lower for BCS (189 mg/kg). Manganese of these samples is similar for each site. For paired samples, Pearson Product Moment Correlation tests reveal that many PAHs are strongly associated with each other at all locations. For BCS alluvium and BSJ sediments, total PAHs are not significantly associated with total metals. For CTY, most pairs of metals are significantly associated, and total soil PAHs are strongly associated with total soil metals (correlation 0.78, P = 4.9 x 10(-4)). The linear model, total soil PAH = 136.3 + 6.25 (total soil metals) forms the basis for a predicted PAH map of New Orleans. Previous empirical research demonstrates an association between soil lead and children's lead exposure. This study indicates that PAHs are part of the soil mixture of accumulated substances and by-products of industrial society that presents exposure potential in cities.

The Erve virus: possible mode of transmission and reservoir.

The Erve virus is suspected to cause severe headache in humans, lasting several days (thunderclap headache). Mice are characterized as a probable reservoir for the Erve virus. We tested 396 wild mice for Erve virus using an immunofluorescence test and found Erve virus antibodies in five cases, showing that small mammals form a reservoir for Erve virus. If ticks are the vector for the virus, a coincidence with borreliosis should exist. We were unable to confirm this in a homogeneous cohort of 955 young men, 62 of whom tested positive for borreliosis. This group did not test positive significantly more often in the immunofluorescence test than a gender- and age-matched control group.

Quantities and associations of lead, zinc, cadmium, manganese, chromium, nickel, vanadium, and copper in fresh Mississippi delta alluvium and New Orleans alluvial soils.

The topic of this study is the effect of anthropogenic metals on the geochemical quality of urban soils. This is accomplished by comparing the metal contents and associations between two alluvial soils of the lower Mississippi River Delta, freshly deposited alluvial parent materials and alluvial soils collected from a nearby urban environment. Fresh alluvium samples (n = 97) were collected from the Bonnet Carré Spillway. The urban alluvial soil samples (n = 4026) were collected from New Orleans and stratified by census tracts (n = 286). The Spillway samples tend to have less Pb and Zn than generally noted for the baseline of natural soils. Except for Mn and V, Spillway alluvium contains significantly less metal than urban soils. For Spillway samples, the median metal content (in microg g(-1)) is 4.7 Pb, 11.1 Zn, 0.7 Cd, 164 Mn, 0.8 Cr, 3.9 Ni, 3.2 V, and 3.9 Cu. For urban soils, the median metal content (in microg g(-1)) is 120 Pb, 130 Zn, 3.2 Cd, 138 Mn, 2.1 Cr, 9.8 Ni, 3.8 V, and 12.7 Cu. Metal associations also differ between Spillway alluvium and urban alluvial soils. Fresh alluvium correlation coefficients between individual metals vary from 0.87 to 0.99 (P < 10(-13)) except for Cr which ranges from 0.57 to 0.68 (P < 10(-7)). The urban soil correlation coefficients for metals and the index value are 0.40-0.98. In urban soils, Pb, Zn, Cr, and Cu are dominant metals and highly associated, with a correlation coefficient ranging from 0.83 to 0.98 (P < 10(-25)). Their strong association justifies the use of GIS to map the integrated soil metal index (sum of the medians of metals by census tract) of New Orleans. Although also positively correlated (0.40-0.68, P < 10(-10)), Cd, Mn, Ni and V differ in their distribution in the city compared to Pb, Zn, Cr and Cu. Overall, significantly higher metal values occur in the inner city and lower values occur in outlying areas. The human health impact of the mixture of metals is not well understood. This study provides empirical data about the mixture and distribution of metals in New Orleans alluvial soils. Given common technical development, especially of traffic flows in cities, similar patterns of soil metals are expected for all US cities and probably international cities as well. Primary prevention of urban metal accumulations is necessary to enhance and sustain the development of urban culture.

The urban environment and children's health: soils as an integrator of lead, zinc, and cadmium in New Orleans, louisiana, U.S.A.

Soils are evaluated as a diagnostic tool of environmental conditions that influence health. The samples for this study are urban topsoil (0-2.5 cm depth) samples (n=4026) analyzed for Pb, Zn, and Cd by inductively coupled plasma-atomic emission spectrometry (ICP-AES). The parent materials for New Orleans soils are derived from the Mississippi River, and alluvium from the Bonnet Carré Spillway (n=31) serve as control samples for this study. The urban samples were stratified by census tract (n=286). Blood Pb (BL) levels of children /=310 microgram g(-1) and <310 microgram g(-1)) for higher metal census tracts (HMCTs) and lower metal census tracts (LMCTs), respectively, represents median BL exposures above and below 9 microgram dL(-1). HMCTs and LMCTs were characterized by demographic and socioeconomic data. HMCTs are more likely (P=4. 5x10(-6)) inhabited by Blacks than by Whites. Of 13,803 children

Soil is an important pathway of human lead exposure.

This review shows the equal or greater importance of leaded gasoline-contaminated dust compared to lead-based paint to the child lead problem, and that soil lead, resulting from leaded gasoline and pulverized lead-based paint, is at least or more important than lead-based paint (intact and not pulverized) as a pathway of human lead exposure. Because lead-based paint is a high-dose source, the biologically relevant dosage is similar to lead in soil. Both lead-based paint and soil lead are associated with severe lead poisoning. Leaded gasoline and lead in food, but not lead-based paint, are strongly associated with population blood lead levels in both young children and adults. Soil lead and house dust, but not lead-based paint, are associated with population blood lead levels in children. Most soil lead and house dust are associated with leaded gasoline. Lead-based paint dust is associated with cases of renovation of either exterior or interior environments in which the paint was pulverized. Based upon the limited data to date, abatement of soil lead is more effective than abatement of lead-based paint in reducing blood lead levels of young children. About equal numbers of children under 7 years of age are exposed to soil lead and lead-based paint. Seasonality studies point to soil lead as the main source of population blood lead levels. Soil lead is a greater risk factor than lead-based paint to children engaged in hand-to-mouth and pica behavior. In summary, soil lead is important for addressing the population of children at risk of lead poisoning. When soil lead is acknowledged by regulators and the public health community as an important pathway of human lead exposure, then more effective opportunities for improving primary lead prevention can become a reality.

Associations between soil lead and childhood blood lead in urban New Orleans and rural Lafourche Parish of Louisiana.

This study evaluates associations between soil lead concentrations (SPb), age of housing, and blood lead levels (BPb) of children in metropolitan New Orleans and Lafourche Parish, Louisiana. The database includes over 2,600 SPb and 6,000 BPb samples paired by their median values and pre-1940 housing percentages for 172 census tracts. Associations were evaluated with Fisher's exact test and Spearman's rho test and modeled with the least sum of absolute deviations regression. Census tracts with low SPb are associated with new housing, but census tracts with high SPb are evenly split between old and new housing [Fisher's exact test, p = 8.60 X 10(-13) for the percentage of housing built before 1940 (percent pre-1940 housing) versus SPb]. The p-value for SPb versus BPb is 12 orders of magnitude stronger than the p-value for percent pre-1940 housing versus BPb. Census tracts with low BPb are associated with new housing, but census tracts with high BPb are split evenly between old and new housing (Fisher's exact test, p = 1. 67 X 10(-12) for percent pre-1940 housing versus BPb). Census tracts with high SPb are associated with high BPb and census tracts with low SPb are associated with low BPb (Fisher's exact test, p = 3.18 X 10(-24) for BPb versus SPb). The Spearman's rho test of the association of SPb and BPb in Orleans and Lafourche Parishes yielded a p-value of 6.12 X 10(-24). The least sum of absolute deviations regression model of the data is BPb = 1. 845 + 0.7215 (SPb)0.4. A comparison of the modeled BPb versus observed BPb has an r(2) of 0.552 and a p-value of 2.83 X 10(-23) that this relation was due to chance. If blood lead in children is more closely associated to soil lead than to the age of housing, then primary lead prevention should also include soil lead.

Environmental health in minority and other underserved populations: Benign methods for identifying lead hazards at day care centres of New Orleans.

This study tests the hypothesis that exterior sources of lead dust are more important than interior sources in the route of exposure of children. Benign field methods were used to distinguish between potential and actual lead exposure problems. Utilising hand wipe and surface wipe techniques, hand and environmental samples were obtained from selected day care centres at different locations within New Orleans. Previous research has shown that soil lead is determined by location within the city. Private and public day care centres were selected from inner and outer city areas to estimate the extent of hand lead exposure. To measure and identify the extent of environmental lead exposure, hand wipes were taken before and after playing outdoors. Results of preliminary findings show that outdoor lead dust is a more potent contaminant of hands than indoor lead dust. An association was found between the amount of lead on children's hands after playing outdoors and the lead content in the exterior dust and soil. Although two girls out of forty children had exceptionally high hand lead quantities after playing outdoors, in general, boys have higher hand lead levels than girls. The private inner-city day care centre had a severe contamination problem in its outdoor play area. By contrast, the outdoor play area of the public inner city day care centre is of such a high quality that the quantity of lead dust is independent of location in the city.

Influence of fertilizer and sewage sludge compost on yield and heavy metal accumulation by lettuce grown in urban soils.

Previous research has demonstrated that many urban soils are enriched in Pb, Cd and Zn. Culture of vegetable crops in these soils could allow transfer of potentially toxic metals to foods. 'Tanya' lettuce (Lactuca sativa L.) was grown in pots of five urban garden soils and one control agricultural soil to assess the effect of urban-soil metal enrichment, and the effect of soil amendments, on heavy metal uptake by garden vegetables. The amendments included NPK fertilizer, limestone, Ca(H2PO4)2, and two rates of limed sewage sludge compost. Soil Cd ranged from 0.08 to 9.6 mg kg(-1); soil Zn from 38 to 3490 mg kg(-1); and soil Pb from 12 to 5210 mg kg(-1). Lettuce yield on the urban garden soils was as great as or greater than that on the control soil. Lettuce Cd, Zn and Pb concentrations increased from 0.65, 23, and 2.2 mg kg(-1) dry matter in the control soil to as high as 3.53, 422 and 37.0 mg kg(-1) on the metal-rich urban garden soils. Adding limestone or limed sewage sludge compost raised soil pH and significantly reduced lettuce Cd and Zn, while phosphate fertilizer lowered soil pH and had little effect on Zn but increased Cd concentration in lettuce. Urban garden soils caused a significant increase in lettuce leaf Pb concentration, especially on the highest Pb soil. Adding NPK fertilizer, phosphate, or sludge compost to two high Pb soils lowered lettuce Pb concentration, but adding limestone generally did not. On normally fertilized soils, Pb uptake by lettuce was not exceptionally high until soil Pb substantially exceeded 500 mg kg(-1). Comparing garden vegetables and soil as potential sources of Pb risk to children, it is clear that the risk is greater through ingestion of soil or dust than through ingestion of garden vegetables grown on the soil. Urban dwellers should obtain soil metal analyses before selecting garden locations to reduce Pb risk to their children.