Biomonitoring of mercury,cadmium, and lead exposure in Japanese children: a cross-sectional study

Objectives

To measure current Hg, Cd, and Pb exposure in Japanese children, and to estimate dietary intakes of foods responsible for high body burden.

Methods

Blood, hair, and urine samples were collected from 9 to 10-year-old 229 children in Asahikawa and measured for Hg, Cd, and Pb in these matrices. Diet history questionnaire was used to estimate intake of marine foods and other food items. Hg level was measured by cold vapor atomic absorption spectrometry. Cd and Pb levels were determined with inductively coupled plasma mass spectrometry.

Results

Geometric mean (GM) of blood Hg, Cd, and Pb was 4.55 μg/L, 0.34 μg/L, and 0.96 μg/dL, respectively. Urinary Cd level was 0.34 μg/g creatinine (GM) and hair Hg was 1.31 μg/g (GM). Approximately one-third (35 %) of blood samples had Hg level above the U.S. EPA reference dose (RfD; 5.8 μg/L). Hair Hg level exceeded U.S. EPA RfD (1.2 μg/g) in 59 % samples. Children in the upper quartile of blood Hg level had significantly higher intake of large predatory fish species compared to those in the lower quartile of blood Hg.

Conclusions

Those with high blood Hg level may be explained by more frequent intake of big predatory fish. Cd and Pb exposure is generally low among Japanese children. As no safety margin exists for Pb exposure and high exposure to MeHg is noted in Japanese population; periodic biomonitoring and potential health risk assessment should continue in high-risk populations, notably among children.     

Food intake survey of kindergarten children in Korea: Part 1 food,energy, and nutrient intake

Objectives

Nutrient intakes of children were surveyed at the time when a nation-wide shift took place in the Republic of Korea from agriculture-based to industrialized society. Taking advantage of the survey locations (see below), possible delay in nutritional improvement in rural areas (as compared with that in an urban area) was also examined.

Methods

In total, 108 4- to 6-year-old children (boys and girls in combination) in 4 kindergartens (KGs; 1 in Seoul and 3 in Jeju Island) participated in the survey in 2003–2004. 24-h food duplicate samples were prepared by the mother of each child. Food items in each duplicate sample were separated and coded with reference to the Dietary Reference Intake for Koreans (the 2005 version). Nutrient intake of the day was estimated from the code and weight followed by summation for daily intake.

Results

The children in the KG in Seoul studied were younger, and therefore were smaller in body size than those in other KGs. Thus, it was considered necessary to evaluate nutrient intake not only on a daily basis, but after adjustment for body weight. The AM daily intake of energy (protein in parenthesis) for the 108 children was 1479 kcal (55 g)/day or 69.8 kcal (2.6 g)/kg body weight/day. Evaluation by individual nutrient suggested that the intake was sufficient for almost all nutrients except for sodium and potassium. Sodium and potassium intake (2285 and 1840 mg/day, respectively) was in excess and insufficient, respectively, with potential risk of inducing hypertension later in life.

Conclusions

Inter-KG difference was not remarkable and therefore urban–rural difference was not apparent. Nutrient intakes as a whole appeared to be sufficient urban and rural areas. Nevertheless, excess Na intake coupled with insufficient K intake was a common problem.     

Food intake survey of kindergarten children in Korea: Part 2 increased dietary intake of tin possibly associated with canned foods

Objectives

Dietary intake of tin (Sn) may be increased in some children in kindergartens in Korea. The present study was intended to examine this possibility and clarify the extent of the elevation.

Methods

24-hour food duplicate and spot urine samples were collected in 2003–2004 from 108 4–6-year-old children (boys and girls combined) in 4 kindergartens (1 in Seoul and 3 in Jeju Island), as reported in a previous publication. These samples were employed in the present analyses to examine tin levels in the diet (including beverages) (Sn-D). A portion of the samples were wet-ashed, and the liquid samples were analyzed for Sn by the ICP-MS method. For statistical evaluation, χ² method and Smirnov’s test for extreme value were used.

Results

Sn-D in the 108 cases distributed as extremely biased, and could be divided into two groups, i.e., those with <10 μg Sn/day (accounting for 90 % of the cases), and those with >10 μg/day (for 10 %). Sn-D in the former group was distributed quasi-normally with an AM (median) of 2.9 (2.5) μg/day. The maximum in the latter group was 3012 μg/day. No correlation was detected between Sn-D and Sn in urine (Sn-U). Comparison of the findings with published articles strongly suggested that the high Sn-D was due to consumption of foods (including beverages) preserved in tin-plated cans. No positive confirmation was however possible due to insufficient information on food records.

Conclusions

About 10 % of children surveyed had elevated Sn-D (up to 3 mg/day). It was quite possible that high Sn-D was associated with tin-canned food intake.     

Association between Lead and Cadmium and Reproductive Hormones in Peripubertal U.S. Girls

Background

Lead (Pb) and cadmium (Cd) are known reproductive toxicants thought to disrupt hormone production throughout sensitive developmental windows, although this has not been previously examined in nationally representative peripubertal children.

Objectives

We examined the association between blood Pb and urinary Cd concentrations and the reproductive hormones inhibin B and luteinizing hormone (LH) in girls 6–11 years of age who participated in the cross-sectional Third National Health and Nutrition Examination Survey (NHANES III) (1988–1994).

Methods

Pb (micrograms per deciliter) was measured in whole blood, and Cd was measured in urine (nanograms per milliliter). Inhibin B (picograms per milliliter) and LH (milli–International units per milliliter) were measured in residual sera for 705 girls. Survey logistic regression was used to estimate associations with pubertal onset based on inhibin B concentration > 35 pg/mL or LH concentration > 0.4 mIU/mL, and multinomial logistic regression was used to estimate the association between Pb and increasing categories of hormone concentrations.

Results

High Pb (≥ 5 μg/dL) was inversely associated with inhibin B > 35 pg/mL [odds ratio (OR) = 0.26; 95% confidence interval (CI), 0.11–0.60; compared with Pb < 1 μg/dL]. At 10 and 11 years of age, girls with low Pb (< 1 μg/dL) had significantly higher inhibin B than did girls with moderate (1–4.99 μg/dL) or high Pb (≥ 5 μg/dL). In the subsample of 260 girls with levels of inhibin B above the level of detection and using survey regression modeling, inhibin B levels were lower among girls with both high Pb and high Cd (β = −0.52; 95% CI, −0.09 to −1.04) than among girls with high Pb alone (β = −0.35; 95% CI, −0.13 to −0.57), relative to girls with low Pb and low Cd.

Conclusions

Higher Pb was inversely associated with inhibin B, a marker of follicular development, and estimated effects suggestive of pubertal delays appeared to be stronger in the context of higher Cd concentrations. These data underscore the importance of Pb and Cd as reproductive toxicants for young girls.     

Windblown Lead Carbonate as the Main Source of Lead in Blood of Children from a Seaside Community: An Example of Local Birds as “Canaries in the Mine”

Background

In late 2006, the seaside community in Esperance, Western Australia, was alerted to thousands of native bird species dying. The source of the lead was thought to derive from the handling of Pb carbonate concentrate from the Magellan mine through the port of Esperance, begun in July 2005. Concern was expressed for the impact of this process on the community.

Objective

This study was designed to evaluate the source of Pb in blood of a random sample of the community using Pb isotope ratios.

Methods

The cohort comprised 49 children (48 < 5 years of age) along with 18 adults (> 20 years of age) with a bias toward higher blood lead (PbB) values to facilitate source identification.

Results

Mean PbB level of the children was 7.5 μg/dL (range, 1.5–25.7 μg/dL; n = 49; geometric mean, 6.6 μg/dL), with four children whose PbB was > 12 μg/dL. The isotopic data for blood samples lay around two distinct arrays. The blood of all children analyzed for Pb isotopes contained a contribution of Pb from the Magellan mine, which for young children ranged from 27% up to 93% (mean, 64%; median, 71%). Subtraction of the ore component gave a mean background PbB of 2.3 μg/dL. Several children whose PbB was > 9 μg/dL and most of the older subjects have complex sources of Pb.

Conclusions

The death of the birds acted as a sentinel event; otherwise, the exposure of the community, arising from such a toxic form of Pb, could have been tragic. Isotopic data and mineralogic and particle size analyses indicate that, apart from the recognized pathway of Pb exposure by hand-to-mouth activity in children, the inhalation pathway could have been a significant contributor to PbB for some of the very young children and in some parents.     

High human exposure to pyrene (polycyclic aromatic hydrocarbon) in Kinshasa,a capital of the Democratic Republic of Congo

Background

Data on human exposure to chemicals in Africa are scarce. A biomonitoring study was conducted in a representative sample of the population in Kinshasa (Democratic Republic of Congo) to document exposure to polycyclic aromatics hydrocarbons.

Methods

1-hydroxypyrene (1-OHP) was measured by HPLC fluorescence in spot urine samples from 220 individuals (50.5% women), aged 6–70 years living in the urban area and from 50 additional subjects from the sub-rural area of Kinshasa. Data were compiled as geometric means and selected percentiles, expressed without (μg/L) or with creatinine adjustment (μg/g cr). Multiple regression analyses were applied to factors (creatinine, grilled meat habits and smoking habits) influencing 1-OHP (stepwise procedure, criteria: probability F to enter ≤ 0.05 and probability F to remove ≥ 0.10).

Results

According to the regression models, creatinine, grilled meat habits and smoking habits contribute to explain 45% of the variation in population’s urinary 1-OHP by the environmental exposure. Overall, living in urban area of Kinshasa was associated with increased levels of 1-OHP in urine as compared to a population living in the sub-rural area [GM: 1.8 μg/L (n = 220) versus 1.4 μg/L (n = 50), p < 0.01] as well as compared to the reference values from databases involving American or German populations.

Conclusion

This study reveals the high pyrene (PAH) exposure of the Kinshasa population. However, more work, with a rigorous design in the exposed population (monitoring of air concentrations and identifying other sources of pyrene –PAH exposure), is needed to establish further documentation.     

Improved HPLC Method Using 2,3-naphthalenedicarboxaldehyde as Fluorescent Labeling Agent for Quantification of Histamine in Human Immunoglobulin Preparations

Objectives

To develop and optimize quantitative HPLC method using 2,3-naphthalenedicarboxaldehyde (NDA) after simple and efficient solid phase extraction to determine the histamine in a biopharmaceutical (Histobulin™).

Methods

The HPLC method was established using NDA-induced Histobulin and compared with the recently reported HPLC method using o-phthaldehyde (OPA). The validated NDA-applied HPLC method was adjusted to 15 lots of Histobulin and compared by the current lot-release-test method using fluorimetry in recovery of histamine and reproducibility.

Results

Analyses of six HPLC chromatograms using NDA and OPA each were compared. NDA produced a more stable chromatogram baseline than OPA, and showed better stability. The HPLC analysis was validated in accuracy (91–103%), precision (interday/intraday assay CV ≤2.30%), and linearity of dose–response curve (R² ≥ 0.9919). The detection limit was 0.0076 μg/mL and the quantitative limit was 0.0229 μg/mL. The amount of histamine per 12 mg of immunoglobulin was determined to be 0.17 ± 0.016 μg by the HPLC and 0.025 ± 0.013 μg by the current lot-release-test method using fluorimetry.

Conclusion

NDA derivatization showed better stability compared with the OPA method. Therefore the newly established NDA-derivatizated HPLC method may be more suitable than the fluorimetric method in lot-release-tests of biopharmaceuticals.     

A revised method for determination of dialkylphosphate levels in human urine by solid-phase extraction and liquid chromatography with tandem mass spectrometry: application to human urine samples from Japanese children

Objectives

Biological monitoring of organophosphorus insecticide (OP) metabolites, specifically dialkylphosphates (DAP) in urine, plays a key role in low-level exposure assessment of OP in individuals. The aims of this study are to develop a simple and sensitive method for determining four urinary DAPs using high-performance liquid chromatography with tandem mass spectrometry (LC–MS/MS), and to assess the concentration range of urinary DAP in Japanese children.

Methods

Deuterium-labeled DAPs were used as internal standards. Urinary dimethylphosphate (DMP) and diethylphosphate (DEP), which passed through the solid-phase extraction (SPE) column, and dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP), which were extracted from a SPE column using 2.5 % NH₃ water including 50 % acetonitrile, were prepared for separation analysis. The samples were then injected into LC–MS/MS. The optimized method was applied to spot urine samples from 3-year-old children (109 males and 116 females) living in Aichi Prefecture in Japan.

Results

Results from the validation study demonstrated good within- and between-run precisions (<10.7 %) with low detection limits (0.4 for DMP and DMTP, 0.2 for DEP and 0.1 μg/L for DETP). The geometric mean values and detection rates of the urinary DAPs in Japanese children were 14.4 μg/L and 100 % for DMP, 5.3 μg/L and 98 % for DMTP, 5.5 μg/L and 99 % for DEP, and 0.6 μg/L and 80 % for DETP, respectively.

Conclusions

The present high-throughput method is simple and reliable, and can thereby further contribute to development of an exposure assessment of OP. The present study is the first to reveal the DAP concentrations in young Japanese children.     

Use of a Cumulative Exposure Index to Estimate the Impact of Tap Water Lead Concentration on Blood Lead Levels in 1- to 5-Year-Old Children (Montréal,Canada)

Background

Drinking water is recognized as a source of lead (Pb) exposure. However, questions remain about the impact of chronic exposure to lead-contaminated water on internal dose.

Objective

Our goal was to estimate the relation between a cumulative water Pb exposure index (CWLEI) and blood Pb levels (BPb) in children 1–5 years of ages.

Methods

Between 10 September 2009 and 27 March 2010, individual characteristics and water consumption data were obtained from 298 children. Venous blood samples were collected (one per child) and a total of five 1-L samples of water per home were drawn from the kitchen tap. A second round of water collection was performed between 22 June 2011 and 6 September 2011 on a subsample of houses. Pb analyses used inductively coupled plasma mass spectroscopy. Multiple linear regressions were used to estimate the association between CWLEI and BPb.

Results

Each 1-unit increase in CWLEI multiplies the expected value of BPb by 1.10 (95% CI: 1.06, 1.15) after adjustment for confounders. Mean BPb was significantly higher in children in the upper third and fourth quartiles of CWLEI (0.7–1.9 and ≥ 1.9 μg/kg of body weight) compared with the first (< 0.2 μg/kg) after adjusting for confounders (19%; 95% CI: 0, 42% and 39%; 95% CI: 15, 67%, respectively). The trends analysis yielded a p-value < 0.0001 after adjusting for confounders suggesting a dose–response relationship between percentiles of CWLEI and BPb.

Conclusions

In children 1–5 years of age, BPb was significantly associated with water lead concentration with an increase starting at a cumulative lead exposure of ≥ 0.7 μg Pb/kg of body weight. In this age group, an increase of 1 μg/L in water lead would result in an increase of 35% of BPb after 150 days of exposure.

Citation

Ngueta G, Abdous B, Tardif R, St-Laurent J, Levallois P. 2016. Use of a cumulative exposure index to estimate the impact of tap water lead concentration on blood lead levels in 1- to 5-year-old children (Montreal, Canada). Environ Health Perspect 124:388–395; http://dx.doi.org/10.1289/ehp.1409144     

Selecting Adequate Exposure Biomarkers of Diisononyl and Diisodecyl Phthalates: Data from the 2005–2006 National Health and Nutrition Examination Survey

Background

High-molecular-weight phthalates, such as diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers.

Objectives

We assessed exposure to DINP and DIDP in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005–2006 National Health and Nutrition Examination Survey (NHANES).

Methods

We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography–tandem mass spectrometry.

Results

We detected monocarboxyisooctyl phthalate (MCOP), a metabolite of DINP, and monocarboxyisononyl phthalate (MCNP), a metabolite of DIDP, in 95.2% and 89.9% of the samples, respectively. We detected monoisononyl phthalate (MNP), a minor metabolite of DINP, much less frequently (12.9%) and at concentration ranges (> 0.8 μg/L–148.1 μg/L) much lower than MCOP (> 0.7 μg/L– 4,961 μg/L). Adjusted geometric mean concentrations of MCOP and MCNP were significantly higher (p < 0.01) among children than among adolescents and adults.

Conclusions

The general U.S. population, including children, was exposed to DINP and DIDP. In previous NHANES cycles, the occurrence of human exposure to DINP by using MNP as the sole urinary biomarker has been underestimated, thus illustrating the importance of selecting the most adequate biomarkers for exposure assessment.     

The U.S. Food and Drug Administration Risk Assessment on Lead in Women’s and Children’s Vitamins Is Based on Outdated Assumptions

Background

Following a recent report of lead in certain commercial vitamin products, the U.S. Food and Drug Administration (FDA) conducted a nationwide survey to determine the Pb content in 324 multivitamin/mineral products labeled for use by women and children. The FDA compared estimated Pb exposures from each product with safe/tolerable exposure levels, termed provisional total tolerable intake (PTTI) levels, previously developed for at-risk population groups in 1992.

Objective

We investigated the FDA’s conclusions that Pb concentrations in all vitamin products examined do not pose a hazard to health because they are below the PTTI levels for all groups considered.

Discussion

For their initial estimations of PTTI levels, the FDA used a blood lead level (BLL) of 10 μg/dL as the threshold for adverse effects in children and in pregnant or lactating women. Studies have repeatedly linked chronic exposure to BLLs < 10 μg/dL with impairments in cognitive function and behavior in young children despite the absence of overt signs of toxicity. The FDA analysis also omitted any consideration of nonfood sources of Pb exposure, which is inconsistent with our current understanding of how most children develop elevated BLLs.

Conclusion

We feel that based on these oversights, the FDA’s conclusions are unduly reassuring and that reconsideration of their current recommendations appears warranted.     

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh

Objectives

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content.

Methods

The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry.

Results

The median iAs concentration in drinking water was 55 μgAs/L (range <0.5–332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7–32.3), 1.8 (<0.5–3.3), 13.7 (5.6–25.0), and 88.6 μgAs/L (47.9–153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water.

Conclusions

All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.     

Blood lead levels in children after phase-out of leaded gasoline in Kinshasa,the capital of Democratic Republic of Congo (DRC)

Background

The phasing out of lead from gasoline has resulted in a significant decrease in blood lead levels (BLLs) in children during the last two decades. Tetraethyl lead was phased out in DRC in 2009. The objective of this study was to test for reduction in pediatric BLLs in Kinshasa, by comparing BLLs collected in 2011 (2 years after use of leaded gasoline was phased out) to those collected in surveys conducted in 2004 and 2008 by Tuakuila et al. (when leaded gasoline was still used).

Methods

We analyzed BLLs in a total of 100 children under 6 years of age (Mean ± SD: 2.9 ± 1.6 age, 64% boys) using inductively coupled argon plasma mass spectrometry (ICP – MS).

Results

The prevalence of elevated BLLs (≥ 10 μg/dL) in children tested was 63% in 2004 [n = 100, GM (95% CI) = 12.4 μg/dL (11.4 – 13.3)] and 71% in 2008 [(n = 55, GM (95% CI) = 11.2 μg/dL (10.3 – 14.4)]. In the present study, this prevalence was 41%. The average BLLs for the current study population [GM (95% CI) = 8.7 μg/dL (8.0 – 9.5)] was lower than those found by Tuakuila et al. (F = 10.38, p <0.001) as well as the CDC level of concern (10 μ/dL), with 3% of children diagnosed with BLLs ≥ 20 μg/dL.

Conclusion

These results demonstrate a significant success of the public health system in Kinshasa, DRC-achieved by the removal of lead from gasoline. However, with increasing evidence that adverse health effects occur at BLLs < 10 μg/dL and no safe BLLs in children has been identified, the BLLs measured in this study continue to constitute a major public health concern for Kinshasa. The emphasis should shift to examine the contributions of non-gasoline sources to children’s BLLs: car batteries recycling in certain residences, the traditional use of fired clay for the treatment of gastritis by pregnant women and leaded paint.     

Air Pollution and Childhood Respiratory Allergies in the United States

Background

Childhood respiratory allergies, which contribute to missed school days and other activity limitations, have increased in recent years, possibly due to environmental factors.

Objective

In this study we examined whether air pollutants are associated with childhood respiratory allergies in the United States.

Methods

For the approximately 70,000 children from the 1999–2005 National Health Interview Survey eligible for this study, we assigned between 40,000 and 60,000 ambient pollution monitoring data from the U.S. Environmental Protection Agency, depending on the pollutant. We used monitors within 20 miles of the child’s residential block group. We used logistic regression models, fit with methods for complex surveys, to examine the associations between the reporting of respiratory allergy or hay fever and annual average exposure to particulate matter ≤ 2.5 μm in diameter (PM_2.5), PM ≤ 10 μm in diameter, sulfur dioxide, and nitrogen dioxide and summer exposure to ozone, controlling for demographic and geographic factors.

Results

Increased respiratory allergy/hay fever was associated with increased summer O₃ levels [adjusted odds ratio (AOR) per 10 ppb = 1.20; 95% confidence interval (CI), 1.15–1.26] and increased PM_2.5 (AOR per 10 μg/m³ = 1.23; 95% CI, 1.10–1.38). These associations persisted after stratification by urban–rural status, inclusion of multiple pollutants, and definition of exposures by differing exposure radii. No associations between the other pollutants and the reporting respiratory allergy/hay fever were apparent.

Conclusions

These results provide evidence of adverse health for children living in areas with chronic exposure to higher levels of O₃ and PM_2.5 compared with children with lower exposures.     

Coarse particulate matter and emergency ambulance dispatches in Fukuoka,Japan: a time-stratified case-crossover study

Objectives

There is no conclusive evidence of adverse health effects caused by short-term exposure to coarse particulate matter, so in this case-crossover study we looked for an association between exposure and emergency ambulance dispatches (as a proxy of acute health outcomes).

Methods

We used data on emergency ambulance dispatches in Fukuoka City, Japan between 2005 and 2010. After excluding ambulance dispatches related to external injuries and pregnancy/childbirth, we analyzed data on 176,123 dispatches. Citywide daily mean concentrations of suspended particulate matter (SPM) and fine particulate matter (PM_2.5) were calculated from ambient monitoring data, and the differences between concentrations of SPM and PM_2.5 were used as an exposure surrogate of coarse particulate matter. Using a conditional logistic regression model, we estimated the ambient temperature and relative humidity adjusted odds ratios (ORs) per 10 μg/m³ increase in coarse particulate matter.

Results

The average daily concentration of coarse particulate matter over the study period was 9.9 μg/m³, representing 33 % of the total concentration of SPM. Elevated concentrations of coarse particulate matter were associated with an increase in respiratory disease-related emergency ambulance dispatches for adults aged 65 years or older (9,716 dispatches, OR for lag0–1 = 1.065, 95 % confidence interval = 1.023–1.109). After additional adjustment for exposure to PM_2.5, we observed a statistically non-significant increased risk (OR = 1.035, 0.986–1.086).

Conclusions

We found weak evidence of adverse effects of short-term exposure to coarse particulate matter on human health.     

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

Background

Concern over phthalates has emerged because of their potential toxicity to humans.

Objective

We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning.

Methods

This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers.

Results

We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables.

Conclusion

Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.     

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua,Mexico

Background

Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures.

Objective

This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk.

Methods

We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine.

Results

After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine.

Conclusions

Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol.

Citation

Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.1408742     

Cadmium and Proliferation in Human Uterine Leiomyoma Cells: Evidence of a Role for EGFR/MAPK Pathways but Not Classical Estrogen Receptor Pathways

Background:

It has been proposed that cadmium (Cd) is an environmental “metalloestrogen” and that its action is mediated via the estrogen receptor (ER). Cd mimics the effects of estrogen in the rat uterus, and blood Cd concentrations positively correlate with ER levels in uteri of women with fibroids.

Objectives:

In the present study we explored whether Cd could stimulate proliferation of estrogen-responsive human uterine leiomyoma (ht-UtLM) cells and uterine smooth muscle cells (ht-UtSMCs) through classical interactions with ERα and ERβ, or by nongenomic mechanisms.

Methods:

We used estrogen response element (ERE) reporters, phosphorylated receptor tyrosine kinase arrays, Western blot analysis, estrogen binding, and cell proliferation assays to evaluate the effects of Cd on ht-UtLM cells and ht-UtSMCs.

Results:

Cd stimulated growth of both cell types at lower concentrations and inhibited growth at higher concentrations (≥ 50 μM). Cd did not significantly bind to ERα or ERβ, nor did it show transactivation in both cell types transiently transfected with ERE reporter genes. However, in both cells types, Cd (0.1 μM and 10 μM) activated p44/42 MAPK (ERK1/2), and a MAPK inhibitor (PD98059) abrogated Cd-induced cell proliferation. Cd in ht-UtLM cells, but not in ht-UtSMCs, activated the growth factor receptors EGFR, HGFR, and VEGF-R1 upstream of MAPK. Additional studies in ht-UtLM cells showed that AG1478, an EGFR inhibitor, abolished Cd-induced phosphorylation of EGFR and MAPK.

Conclusions:

Our results show that low concentrations of Cd stimulated cell proliferation in estrogen-responsive uterine cells by nongenomic activation of MAPK, but not through classical ER-mediated pathways.

Citation:

Gao X, Yu L, Moore AB, Kissling GE, Waalkes MP, Dixon D. 2015. Cadmium and proliferation in human uterine leiomyoma cells: evidence of a role for EGFR/MAPK pathways but not classical estrogen receptor pathways. Environ Health Perspect 123:331–336; http://dx.doi.org/10.1289/ehp.1408234     

Urine Arsenic Concentrations and Species Excretion Patterns in American Indian Communities Over a 10-year Period: The Strong Heart Study

Background

Arsenic exposure in drinking water disproportionately affects small communities in some U.S. regions, including American Indian communities. In U.S. adults with no seafood intake, median total urine arsenic is 3.4 μg/L.

Objective

We evaluated arsenic exposure and excretion patterns using urine samples collected over 10 years in a random sample of American Indians from Arizona, Oklahoma, and North and South Dakota who participated in a cohort study from 1989 to 1999.

Methods

We measured total urine arsenic and arsenic species [inorganic arsenic (arsenite and arsenate), methylarsonate (MA), dimethylarsinate (DMA), and arsenobetaine] concentrations in 60 participants (three urine samples each, for a total of 180 urine samples) using inductively coupled plasma/mass spectrometry (ICPMS) and high-performance liquid chromatography/ICPMS, respectively.

Results

Median (10th, 90th percentiles) urine concentration for the sum of inorganic arsenic, MA, and DMA at baseline was 7.2 (3.1, 16.9) μg/g creatinine; the median was higher in Arizona (12.5 μg/g), intermediate in the Dakotas (9.1 μg/g), and lower in Oklahoma (4.4 μg/g). The mean percentage distribution of arsenic species over the sum of inorganic and methylated species was 10.6% for inorganic arsenic, 18.4% for MA, and 70.9% for DMA. The intraclass correlation coefficient for three repeated arsenic measurements over a 10-year period was 0.80 for the sum of inorganic and methylated species and 0.64, 0.80, and 0.77 for percent inorganic arsenic, percent MA, and percent DMA, respectively.

Conclusions

This study found low to moderate inorganic arsenic exposure and confirmed long-term constancy in arsenic exposure and urine excretion patterns in American Indians from three U.S. regions over a 10-year period. Our findings support the feasibility of analyzing arsenic species in large population-based studies with stored urine samples.     

New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

Objective

To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.

Methods

We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.

Findings

In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).

Conclusion

The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.