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1.  Multiple classes of environmental chemicals are associated with liver disease: NHANES 2003–2004 
Biomonitoring studies show that humans carry a body burden of multiple classes of contaminants which are not often studied together. Many of these chemicals may be hepatotoxic. We used the 2003–2004 National Health and Nutrition Examination Survey to evaluate the relationship between alanine aminotransferase (ALT) and 37 environmental contaminants, comprising heavy metals, non-dioxin-like polychlorinated biphenyls (PCBs), and dioxin-like compounds, using a novel method. Linear regression models were constructed for each chemical separately, then as a class, using quartiles to represent exposure and adjusting for age, sex, race, income, and BMI. We then used an optimization approach to compile a weighted sum of the quartile scores, both within and across chemical classes. Using the optimization approach to construct weighted quartile scores, the dioxin like PCB, the non-dioxin like PCB and metal class-level scores were significantly associated with elevated ALT. A significant interaction was detected between the class-level score for metals, and the score for non-dioxin-like PCBs. When including all chemicals in one model, 3 chemicals accounted for 78 % of the weight (Mercury, PCB 180, 3,3’,4,4’,5-PNCB) with the remaining 22% associated with 4 chemicals (a dioxin and 3 PCBs). Validation with a holdout dataset indicated that the weighted quartile sum estimator efficiently identifies reproducible significant associations.
PMCID: PMC3713174  PMID: 23491026
Biomonitoring; ALT; liver; mixtures; cumulative
Over the last decades many epidemiologic studies considered the morbidity patterns for respiratory diseases and lung function of children in the context of ambient air pollution usually measured in the postnatal period. The main purpose of this study is to assess the impact of prenatal exposure to fine particulate matter (PM2.5) on the recurrent broncho-pulmonary infections in early childhood.
The study included 214 children who had measurements of personal prenatal PM2.5 exposure and regularly collected data on the occurrence of acute bronchitis and pneumonia diagnosed by a physician from birth over the seven-year follow-up. The effect of prenatal exposure to PM2.5 was adjusted in the multivariable logistic models for potential confounders, such as prenatal and postnatal ETS (environmental tobacco smoke), city residence area as a proxy of postnatal urban exposure, children’s sensitization to domestic aeroallergens, and asthma. In the subgroup of children with available PM2.5 indoor levels, the effect of prenatal exposure was additionally adjusted for indoor exposure as well. The adjusted odds ratio (OR) for incidence of recurrent broncho-pulmonary infections (five or more spells of bronchitis and/or pneumonia) recorded in the follow-up significantly correlated in a dose-response manner with the prenatal PM2.5 level (OR = 2.44, 95%CI: 1.12 – 5.36).
In conclusion, the study suggests that prenatal exposure to PM2.5 increases susceptibility to respiratory infections and may program respiratory morbidity in early childhood. The study also provides evidence that the target value of 20 μg/m3 for the 24-hour mean level of PM2.5 protects unborn babies better than earlier established EPA guidelines.
PMCID: PMC3657308  PMID: 23333083
birth cohort study; fine particulate matter; prenatal and postnatal exposure; bronchitis; pneumonia
3.  Methylmercury and elemental mercury differentially associate with blood pressure among dental professionals 
Methylmercury-associated effects on the cardiovascular system have been documented though discrepancies exist, and most studied populations experience elevated methylmercury exposures. No paper has investigated the impact of low-level elemental (inorganic) mercury exposure on cardiovascular risk in humans. The purpose of this study was to increase understanding of the association between mercury exposure (methylmercury and elemental mercury) and blood pressure measures in a cohort of dental professionals that experience background exposures to both mercury forms. Dental professionals were recruited during the 2010 Michigan Dental Association Annual Convention. Mercury levels in hair and urine samples were analyzed as biomarkers of methylmercury and elemental mercury exposure, respectively. Blood pressure (systolic, diastolic) was measured using an automated device. Distribution of mercury in hair (mean, range: 0.45, 0.02–5.18 μg/g) and urine (0.94, 0.03–5.54 μg/L) correspond well with the US National Health and Nutrition Examination Survey. Linear regression models revealed significant associations between diastolic blood pressure (adjusted for blood pressure medication use) and hair mercury (n = 262, p = 0.02). Urine mercury results opposed hair mercury in many ways. Notably, elemental mercury exposure was associated with a significant systolic blood pressure decrease (n = 262, p = 0.04) that was driven by the male population. Associations between blood pressure and two forms of mercury were found at exposure levels relevant to the general population, and associations varied according to type of mercury exposure and gender.
PMCID: PMC3727420  PMID: 22494934
Mercury; Blood pressure; Epidemiology; Gender difference; Environmental exposure
4.  Maternal occupation and the risk of major birth defects: A follow-up analysis from the National Birth Defects Prevention Study 
International journal of hygiene and environmental health  2012;216(3):10.1016/j.ijheh.2012.05.006.
This study further examined the association between selected maternal occupations and a variety of birth defects identified from prior analysis and explored the effect of work hours and number of jobs held and potential interaction between folic acid and occupation. Data from a population-based, multi-center case-control study was used. Analyses included 45 major defects and specific sub-occupations under five occupational groups: healthcare workers, cleaners, scientists, teachers and personal service workers. Both logistic regression and Bayesian models (to minimize type-1 errors) were used, adjusted for potential confounders. Effect modification by folic acid was also assessed. More than any other occupation, nine different defects were positively associated with maids or janitors [odds ratio (OR) range: 1.72-3.99]. Positive associations were also seen between the following maternal occupations and defects in their children (OR range: 1.35-3.48): chemists/conotruncal heart and neural tube defects (NTDs), engineers/conotruncal defects, preschool teachers/cataracts and cleft lip with/without cleft palate (CL/P), entertainers/athletes/gastroschisis, and nurses/hydrocephalus and left ventricular outflow tract heart defects. Non-preschool teachers had significantly lower odds of oral clefts and gastroschisis in their offspring (OR range: 0.53-0.76). There was a suggestion that maternal folic acid use modified the effects with occupations including lowering the risk of NTDs and CL/P. No consistent patterns were found between maternal work hours or multiple jobs by occupation and the risk of birth defects. Overall, mothers working as maids, janitors, biologists, chemists, engineers, nurses, entertainers, child care workers and preschool teachers had increased risks of several malformations and non-preschool teachers had a lower risk of some defects. Maternal folic acid use reduced the odds of NTDs and CL/P among those with certain occupations. This hypothesis-generating study will provide clues for future studies with better exposure data.
PMCID: PMC3824611  PMID: 22695106
occupation; birth defects; folic acid
5.  Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A in pooled urine specimens from pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa) 
Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples representing 110 pregnant women who participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004. Daily intakes were estimated from urinary data and compared with reference doses (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA concentration (4.50 μg/L) than the pregnant women in the Generation R Study (Generation R) in the Netherlands and the National Health and Nutrition Examination Survey (NHANES) in the United States. The mean concentration of total DAP metabolites (24.20 μg/L) in MoBa women was higher than that in NHANES women but lower than that in Generation R women. The diethyl phthalate metabolite mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three studies, with the mean concentrations of greater than 300 μg/L. The MoBa and Generation R women had higher mean concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated average daily intakes of BPA, chlorpyrifos/chlorpyrfios-methyl and phthalates in MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels of metabolites in the MoBa participants may have been from intake via pesticide residues in food (organophosphates), consumption of canned food, especially fish/seafood (BPA), and use of personal care products (selected phthalates).
PMCID: PMC3756471  PMID: 19394271
Organophosphate (OP) pesticides; Bisphenol A (BPA); Phthalates; Biological monitoring; Environmental Exposure
6.  Exposure of flight attendants to pyrethroid insecticides on commercial flights: urinary metabolite levels and implications 
Pyrethroid insecticides have been used for disinsection of commercial aircrafts. However, little is known about the pyrethroids exposure of flight attendants. The objective of the study was to assess pyrethroids exposure of flight attendants working on commercial aircrafts through monitoring the urinary pyrethroids metabolite levels. Eighty four urine samples were collected from 28 flight attendants, 18 – 65 years of age, with seventeen working on planes that were non-disinsected, and eleven working on planes that had been disinsected. Five urinary metabolites of pyrethroids were measured using gas chromatographic–mass spectrometric method: 3-phenoxybenzoic acid (3-PBA), cis-/trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclo-propane carboxylic acid (cis-/trans-Cl2CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclo-propane-1-carboxylic acid (cis-Br2CA) and 4-fluoro-3-phenoxybenzoic acid (4F-3-PBA). Flight attendants working on disinsected planes had significantly higher urinary levels of 3-PBA, cis- and trans-Cl2CA in pre, post- and 24hr-post flight samples than those on planes which did not report having been disinsected. Urinary levels of cis-Br2CA and 4F-3-PBA did not show significant differences between the two groups. Flight attendants working on international flights connected to Australia had higher urinary levels of 3-PBA, cis- and trans-Cl2CA than those on either domestic and other international flights flying among Asia, Europe and North America. Post-disinsection duration (number of days from disinsection date to flight date) was the most significant factor affecting the urinary pyrethroid metabolites levels of 3-PBA, cis- and trans-Cl2CA of the group flying on disinsected aircraft. It was concluded that working on commercial aircrafts disinsected by pyrethroids resulted in elevated body burden of 3-PBA, cis- and trans-Cl2CA.
PMCID: PMC3299936  PMID: 21937269
flight attendant; disinsection; pyrethroid; permethrin; pesticide; metabolite; 3-PBA
7.  Nephrotoxicity, Neurotoxicity, and Mercury Exposure among Children with and without Dental Amalgam Fillings 
International journal of hygiene and environmental health  2008;212(4):10.1016/j.ijheh.2008.09.004.
A scientific review panel for the U.S. Food and Drug Administration (FDA) recently identified the need for more data on the health risk of mercury exposure from dental amalgam among susceptible populations. We evaluated impacts of low level mercury exposure on renal function and neurobehavioral and neuropsychological performance among children.
Dental histories for 403 children aged 7-11 years in five schools from Xuhui, Shanghai were checked by dentists. Of them, 198 with confirmed amalgam fillings were recruited (exposure group). Reference children (N=205) were those who never had dental amalgam treatment. In May 2004, each child provided a urine sample for measurements of total mercury, n-acetyl-β-D-glucosaminidase activity, microalbumin, and creatinine (Cr). The Child Behavior Checklist, Eysenck Personality Questionnaire, and an intelligence screening test were administered.
The geometric mean urinary mercury concentration was 1.6 μg/g Cr for children with and 1.4 μg/g Cr for children without amalgam fillings. No differences were found between children with and without fillings for either renal function biomarker, or on neurobehavioral, neuropsychological, or intelligence tests.
Although urinary mercury concentration was slightly elevated among children with amalgam fillings, we found no evidence of adverse effects on the outcomes evaluated. These results agree with those from recent trials in developed countries.
PMCID: PMC3653184  PMID: 18996050
dental amalgam; mercury; nephrotoxicity; neurotoxicity
8.  Estimation of benchmark dose for micronucleus occurrence in Chinese vinyl chloride-exposed workers☆ 
In this study, we estimated the possibility of using benchmark dose (BMD) to assess the dose–response relationship between vinyl chloride monomer (VCM) exposure and chromosome damage. A group of 317 workers occupationally exposed to vinyl chloride monomer and 166 normal, unexposed control in Shan-dong Province northern China were examined for chromosomal damage in peripheral blood lymphocytes (PBL) using the cytokinesis-blocked micronucleus (CB-MN) assay of DNA damage. The exposed group (3.47 ± 2.65)‰ showed higher micronucleus frequency than the control (1.60 ± 1.30)‰ (P < 0.01). Occupational exposure level based on micronucleus occurrence in all individuals was analyzed with benchmark dose (BMD) methods. The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. Results showed a dose–response relationship between cumulative exposure and MN frequency, and a BMDL of 0.54 mg/m3 and 0.23 mg/m3 for males and females, respectively. Female workers were more susceptible to MN damage than male workers.
PMCID: PMC3404251  PMID: 22425610
Vinyl chloride monomer; Chromosomal damage; Benchmark dose; Micronucleus
9.  Prenatal low-level lead exposure and developmental delay of infants at age 6 months (Krakow inner city study) 
The purpose of the study was to assess the neurocognitive status of 6-month-old infants whose mothers were exposed to low but varying amounts of lead during pregnancy. Lead levels in the cord blood were used to assess environmental exposure and the Fagan Test of Infant Intelligence (FTII) assessed visual recognition memory (VRM). The cohort consisted of 452 infants of mothers who gave birth to babies at 33–42 weeks of gestation between January 2001 and March 2003. The overall mean lead level in the cord blood was 1.42 μg/dl (95% CI: 1.35–1.48). We found that VRM scores in 6 month olds were inversely related to lead cord blood levels (Spearman correlation coefficient −0.16, p = 0.007). The infants scored lower by 1.5 points with an increase by one unit (1 μg/dl) of lead concentration in cord blood. In the lower exposed infants (≤1.67 μg/dl) the mean Fagan score was 61.0 (95% CI: 60.3–61.7) and that in the higher exposed group (>1.67 μg/dl) was 58.4 (95% CI: 57.3–59.7). The difference of 2.5 points was significant at the p = 0.0005 level. The estimated risk of scoring the high-risk group of developmental delay (FTII classification 3) due to higher lead blood levels was two-fold greater (OR = 2.33, 95% CI: 1.32–4.11) than for lower lead blood levels after adjusting for potential confounders (gestational age, gender of the child and maternal education). As the risk of the deficit in VRM score (Fagan group 3) in exposed infants attributable to Pb prenatal exposure was about 50%, a large portion of cases with developmental delay could be prevented by reducing maternal blood lead level below 1.67 μg/dl. Although the negative predictive value of the chosen screening criterion (above 1.67 μg/dl) was relatively high (89%) its positive predictive value was too low (22%), so that the screening program based on the chosen cord blood lead criterion was recommended.
PMCID: PMC3139437  PMID: 17905657
Prenatal lead exposure; Biological markers; Infant visual recognition memory; Neurocognitive development
10.  The relationship between mental retardation and developmental delays in children and the levels of arsenic, mercury and lead in soil samples taken near their mother's residence during pregnancy 
This study was designed to evaluate the association between lead, mercury, and arsenic in the soil near maternal residences during pregnancy and mental retardation or developmental disability (MR/DD) in children. The study was conducted using 6,048 mothers who did not move throughout their pregnancies and lived within six strips of land in South Carolina and were insured by Medicaid between January 1, 1997 and December 31, 2002. The mother child pairs were then followed until June 1, 2008, through their Medicaid reimbursement files, to identify children diagnosed with MR/DD. The soil was sampled for mercury (Hg), lead (Pb), and As based on a uniform grid, and the soil concentrations were Kriged to estimate chemical concentration at individual locations. We identified a significant relationship between MR/DD and As, and the form of the relationship was nonlinear, after controlling for other known risk factors.
PMCID: PMC2836425  PMID: 20045663
Mental retardation/developmental delay; Soil arsenic; Maternal residence; Kriging; Nonlinear
11.  Agricultural Pesticides and Risk of Childhood Cancers 
Agricultural pesticide applications have the potential for significant drift beyond the target spray area and may result in exposure to non-farming residents in surrounding communities. Using geographic information system (GIS) methods, 1778 childhood cancer cases and 1802 controls born in Texas between 1990 and 1998 were assigned probable agricultural pesticide exposure based on proximity of birth residence to crop fields. Multivariate modeling was used to estimate odds ratios and 95 percent confidence intervals for selected cancers. For most childhood cancers, we found no evidence of elevated risk associated with residential proximity at birth to cropland. There was an overall pattern of increased risk for germ cell tumors but the odds ratios were based on few numbers of exposed cases. There was also some indication of increased risk for NHL and Burkitt lymphoma, but point estimates were imprecise and not statistically significant. Previous studies have assessed pesticide exposure primarily based on parental occupational history or household use, while our focus was on agricultural pesticides and so may represent a different array of chemical agents occurring at lower doses.
PMCID: PMC2659586  PMID: 18675586
agriculture; pesticides; childhood cancers; epidemiology
12.  A report of cytokine polymorphisms and COPD risk in Xuan Wei, China 
Indoor air pollution has been documented as an important risk factor for chronic obstructive pulmonary disease (COPD), and inflammation is central to the development and progression of COPD. Single nucleotide polymorphisms (SNP) in some cytokine genes have been reported to be associated with COPD. We examined the association between 18 SNPs in 10 cytokine genes and COPD risk in a case-control study conducted in a population with high exposure to indoor smoky coal emissions. The study included 53 COPD cases and 122 healthy community controls. Carriers of the CSF2 117Ile allele had a 2.4-fold higher risk of COPD than the wild type (Thr/Thr) carriers (OR: 2.44; 95% CI: 1.10 – 5.41), and the AA genotype at IL8 -351 was associated with an increased risk of COPD (OR: 2.71; 95% CI: 1.04 – 7.04). When the combined effects of CSF2 117Ile and IL8 -351A were examined, individuals carrying at least one variant in both genes had a five-fold increased risk of COPD (OR: 5.14, 95% CI: 1.32 – 29.86). This study suggests that polymorphisms in both CSF2 and IL8 may play a role in the pathogenesis of COPD, at least in highly exposed populations. However, in view of our relatively small sample size, this study should be replicated in other populations with substantial exposure to indoor air pollutants such as polycyclic aromatic hydrocarbons (PAH) and particulate matter.
PMCID: PMC2639784  PMID: 17681858
COPD; Cytokine; CSF2; IL8; Single nucleotide polymorphism; Indoor air pollution
13.  Some evidence of effects of environmental chemicals on the endocrine system in children 
Pollutant chemicals that are widespread in the environment can affect endocrine function in laboratory experiments and in wildlife. Although human beings are commonly exposed to such pollutant chemicals, the exposures are generally low and clear effects on endocrine function from such exposures have been difficult to demonstrate. Human data including both exposure to the chemical agent and the endocrine outcome are reviewed here, including age at weaning, age at puberty, anogenital distance, and sex ratio at birth, and the strength of the evidence discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real.
PMCID: PMC2245801  PMID: 17870664
Endrocrine disruptors; Environmental chemicals; Lactation; Thyroid function; Sex ratio; Puberty
14.  Lead levels in blood and saliva in a low-income population of Detroit, Michigan 
The relationships between blood lead (PbB) and saliva lead (PbSa) concentrations and the determinants of PbB and PbSa status in 970 low-income adults in the city of Detroit, Michigan were explored. Average PbB and PbSa values in the sample population were found to be 2.7 ± 0.1 μg/dl and 2.4 ± 0.13 μg/l (equivalent to 0.24 ± 0.13 μg/dl), respectively, and a weak but statistically significant association was found between the lead levels in the two types of body fluid samples. The average PbB level for men (4.0 ± 0.56 μg/dl) was higher than that for women (2.7 ± 0.11 μg/dl); other significant predictors of PbB included age, level of education, being employed, income level, the presence of peeling paint on the wall at home and smoking. There was no gender- or age-dependent difference in blood saliva values but statistically significant correlations were found between PbSa and level of education, employment, income level and smoking. Dental caries was severe in this population. Only 0.5% of the participants had no clinical signs of caries, over 80% had cavitated carious lesions (i.e., lesions that had progressed into dentin), and the number of lost teeth and carious lesions averaged 3.4 and 30, respectively. Weak but significant associations were found between PbB as well as PbSa and measures of dental caries in the study population. The positive associations are believed to be a reflection of the fact that the risk factors for dental caries, especially in low-income populations of the US, overlap extensively with those of lead poisoning and may not have a causal significance.
PMCID: PMC1819402  PMID: 16443391
Blood lead; Saliva lead; Dental caries; Lead exposure; Biomonitoring; Lead poisoning

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