Determinants of urinary concentrations of dialkyl phosphates among pregnant women in Canada — Results from the MIREC study

Organophosphate (OP) insecticides are commonly used in agriculture. Their use decreased in recent years as they were gradually replaced by other pesticides, but some OPs are still among the insecticides most used in Canada. Exposure to elevated levels of OPs during pregnancy has been associated with adverse birth outcomes and poorer neurodevelopment in children. The objective of the present study was to examine the relationship between the concentrations of OP pesticides urinary dialkyl phosphate (DAP) metabolites and various factors that are potential sources of exposure or determinants of DAP levels. In the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, six DAPs were measured in 1st trimester urine samples of 1884 pregnant women living in Canada. They were grouped into sums of dimethyl alkyl phosphates (DMAP) and diethyl alkyl phosphates (DEAP) for statistical analysis. We found that 93% of women had at least one DAP detected in their urine. Geometric means (GM) of specific gravity-corrected levels for urine dilution were 59 (95% CI 56–62) and 21 (95% CI 20–22) nmol/L for DMAP and DEAP, respectively. The following characteristics were significantly associated with higher urinary concentrations of DMAP or DEAP: higher education, nulliparous, normal pre-pregnancy body mass index, non-smoker, not fasting at sampling, winter season at sampling, and early and late day collection times. Dietary items that were significantly related with higher urinary concentrations included higher intake of citrus fruits, apple juice, sweet peppers, tomatoes, beans and dry peas, soy and rice beverages, whole grain bread, white wine and green and herbal teas. This study indicates that exposure to these compounds is quasi-ubiquitous. The factors associated with greater DAP levels identified here could be useful to regulatory agencies for risk analysis and management. However, some exposure misclassification might occur due to the single DAP measurement available, and to the presence of preformed DAPs in the environment.     

Population model of fluctuations in organophosphate resistance of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>: Roles of a mutated acetylcholinesterase and a cytochrome P450

The dynamics of genetic variation in susceptibility to insecticides within a natural population of Drosophila melanogaster (Meigen) was examined using model systems and experimental data published previously. In a recent study, two resistance factors for three organophosphate insecticides (OPs) were suggested to be involved within the Katsunuma population (Yamanashi Prefecture, Japan): a resistant-type acetylcholinesterase (AChE) and a cytochrome P450 monooxygenase (cytochrome P450). Within this natural population, the relative contributions of the resistanttype AChE to genetic variation in resistance to the three OPs were larger than those of the cytochrome P450. The simulation analysis by means of the model, based on genotypic density-independent population projection trajectories, suggested that seasonal fluctuations of genetic variation in resistance to the three OPs were mainly caused by the change in the frequency of the resistant-type acetylcholinesterase (Ace) gene within the population.     

Analysis of the toxicogenomic effects of exposure to persistent organic pollutants (POPs) in Slovakian girls: correlations between gene expression and disease risk

The chemical composition of persistent organic pollutants (POPs) in the environment is not uniform throughout the world, and these contaminants contain many structurally different lipophilic compounds. In a well-defined study cohort in the Slovak Republic, the POP chemicals present in the peripheral blood of exposed children were chemically analyzed. The chemical analysis data revealed that the relative concentration and profile of structurally different organic pollutants, including polychlorinated biphenyls (PCBs), 2,2′-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p′-DDE), 2,2′-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (p,p′-DDT), hexachlorobenzene (HCB) and β-hexachlorocyclohexane (β-HCH), may vary from individual to individual, even within the same exposure area. These chemicals can be broadly classified into two groups. The first group, the PCB congeners, primarily originated from industrial compounds and their byproducts. The second group of compounds originated from or was commonly used in the agricultural sector (e.g., DDT, HCB). The objective of this study was to examine the effects of the two POP exposure profiles on gene expression. For the study population, we selected pre-pubertal girls (mean age of 46.2 ± 1.4 months) with high POP concentrations in their blood (> 75% tile of total POP) and classified them in the high ‘PCB’ group when the total PCB concentration was significantly higher than the total concentration of other POP components and in the ‘Other Than PCB’ (OTP) group, when the total PCB concentration was significantly lower than the concentration of the other major POP constituents. A matched control group of girls (< 25% tile of total POP) was selected for comparison purpose (n = 5 per group). Our aims were to determine whether there were any common effects of high POP exposure at a toxicogenomic level and to investigate how exposure may affect physiological functions of the children in two different exposure scenarios. Global gene expression analysis using a microarray (Affymetrix Gene Chip Human genome U133 Plus 2.0 Array) platform was conducted on the total RNA of peripheral blood mononuclear cells from the girls. The results were analyzed by Partek GS, Louis, MI, which identified twelve genes (ATAD2B, BIVM, CD96, CXorf39, CYTH1 ETNK1, FAM13A, HIRA, INO80B, ODG1, RAD23B, and TSGA14) and two unidentified probe sets, as regulated differentially in both the PCB and OTP groups against the control group. The qRT-PCR method was used to validate the microarray results. The Ingenuity Pathway Analysis (IPA) software package identified the possible molecular impairments and disease risks associated with each gene set. Connective tissue disorders, genetic disorders, skeletal muscular disorders and neurological diseases were associated with the 12 common genes. The data therefore identified the potential molecular effects of POP exposure on a genomic level. This report underscores the importance of further study to validate the results in a random population and to evaluate the use of the identified genes as biomarkers for POP exposure.     

Functional paraoxonase 1 variants modify the risk of Parkinson's disease due to organophosphate exposure

BackgroundWe previously demonstrated that carriers of the “slower metabolizer” MM genotype of paraoxonase (PON1) who were also exposed to ambient organophosphate (OP) pesticides at their residences were at increased risk of developing Parkinson's disease (PD). Here, with a larger sample size, we extend our previous investigation to consider additional sources of ambient exposure and examined two additional functional PON1 variants.MethodsFrom 2001 to 2011, we enrolled incident cases of idiopathic PD and population controls living in central California. We genotyped three well-known functional PON1 SNPs: two exonic polymorphisms (PON1_L55M and PON1_Q192R) and the promoter region variant (PON1_C-108T). Ambient exposures to diazinon, chlorpyrifos, and parathion at residential and workplace addresses were assessed using a validated geographic information system-based model incorporating records of agricultural pesticide applications in California.ResultsThe odds ratio (OR) for Caucasians exposed to OPs at either residential or workplace addresses varied by PON1 genotype; for exposed carriers of the “faster” metabolizer genotypes, ML or LL, we estimated lower odds ratios (range, 1.20–1.39) than for exposed carriers of the “slower” metabolizer genotype MM (range, 1.78–2.45) relative to unexposed carriers of the faster genotypes. We observed similarly increased ORs for exposure across PON1_Q192R genotypes, but no differences across PON1_C-108T genotypes. The largest ORs were estimated for exposed carriers of both PON1_192QQ and PON1_55MM (OR range, 2.84–3.57).ConclusionsSeveral functional PON1 variants may act together to modify PD risk for ambient OP exposures. While either PON1_L55M or PON1_Q192R may be sufficient to identify increased susceptibility, carriers of both slow metabolizer variants seem most susceptible to OP exposures.     

Predictors of exposure to organophosphate pesticides in schoolchildren in the Province of Talca,Chile

BackgroundFew data exist in Latin America concerning the association between organophosphate (OP) urinary metabolites and the consumption of fruits and vegetables and other exposure risk variables in schoolchildren.MethodsWe collected samples of urine from 190 Chilean children aged 6–12 years, fruits and vegetables, water and soil from schools and homes, and sociodemographic data through a questionnaire. We measured urinary dialkylphosphate (DAP) OP metabolites and OP pesticide residues in food consumed by these 190 children during two seasons: December 2010 (summer) and May 2011 (fall). We analyzed the relationship between urinary DAP concentrations and pesticide residues in food, home pesticide use, and residential location.ResultsDiethylalkylphosphates (DEAP) and dimethylalkylphosphates (DMAP) were detected in urine in 76% and 27% of the samples, respectively. Factors associated with urinary DEAP included chlorpyrifos in consumed fruits (p < 0.0001), urinary creatinine (p < 0.0001), rural residence (p = 0.02) and age less than 9 years (p = 0.004). Factors associated with urinary DMAP included the presence of phosmet residues in fruits (p < 0.0001), close proximity to a farm (p = 0.002), home fenitrothion use (p = 0.009), and season (p < 0.0001).ConclusionsUrinary DAP levels in Chilean school children were high compared to previously reported studies. The presence of chlorpyrifos and phosmet residues in fruits was the major factor predicting urinary DAP metabolite concentrations in children.     

mSpray: A mobile phone technology to improve malaria control efforts and monitor human exposure to malaria control pesticides in Limpopo,South Africa

Recent estimates indicate that malaria has led to over half a million deaths worldwide, mostly to African children. Indoor residual spraying (IRS) of insecticides is one of the primary vector control interventions. However, current reporting systems do not obtain precise location of IRS events in relation to malaria cases, which poses challenges for effective and efficient malaria control. This information is also critical to avoid unnecessary human exposure to IRS insecticides. We developed and piloted a mobile-based application (mSpray) to collect comprehensive information on IRS spray events. We assessed the utility, acceptability and feasibility of using mSpray to gather improved homestead- and chemical-level IRS coverage data. We installed mSpray on 10 cell phones with data bundles, and pilot tested it with 13 users in Limpopo, South Africa. Users completed basic information (number of rooms/shelters sprayed; chemical used, etc.) on spray events. Upon submission, this information as well as geographic positioning system coordinates and time/date stamp were uploaded to a Google Drive Spreadsheet to be viewed in real time. We administered questionnaires, conducted focus groups, and interviewed key informants to evaluate the utility of the app. The low-cost, cell phone-based “mSpray” app was learned quickly by users, well accepted and preferred to the current paper-based method. We recorded 2865 entries (99.1% had a GPS accuracy of 20 m or less) and identified areas of improvement including increased battery life. We also identified a number of logistic and user problems (e.g., cost of cell phones and cellular bundles, battery life, obtaining accurate GPS measures, user errors, etc.) that would need to be overcome before full deployment. Use of cell phone technology could increase the efficiency of IRS malaria control efforts by mapping spray events in relation to malaria cases, resulting in more judicious use of chemicals that are potentially harmful to humans and the environment.     

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: A review

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted.     

Alkyl protocatechuates as novel urinary biomarkers of exposure to p-hydroxybenzoic acid esters (parabens)

Human exposure to p-hydroxybenzoic acid esters (parabens) is a concern, owing to adverse health effects of these compounds. Parabens are metabolized and eliminated from the human bodies within a few hours of exposure. In this study, for the first time, methyl- and ethyl-protocatechuates (OH-MeP and OH-EtP) and their parent compounds, methyl- (MeP) and ethyl-parabens (EtP), were determined in urine samples collected from U.S. children and adults. Alkyl protocatechuates were found in almost all urine samples, with median concentrations of 11.8 (OH-MeP) and 2.90 ng/mL (OH-EtP) in adults, and 5.43 (OH-MeP) and 0.85 ng/mL (OH-EtP) in children. In adults, the concentrations of urinary OH-MeP and OH-EtP were higher than the corresponding concentrations of MeP and EtP. Significant correlation between OH-MeP/OH-EtP and MeP/EtP was observed. This is the first report to document hydroxylation of parabens in humans, and to propose hydroxylated metabolites (i.e., alkyl protocatechuates) as alternative biomarkers of exposure to parabens in human biomonitoring studies. The rates of transformation of parabens between children and adults appeared to be different, as evidenced from the slopes of regression between alkyl protocatechuates and parabens. In addition to alkyl protocatechuates, hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were found at considerable levels in the urine samples. The occurrence of a significant proportion of alkyl protocatechuates and 3,4-DHB suggests the need for inclusion of these derivatives in accurate estimation of human exposure to parabens and in epidemiological studies that associate paraben exposure to health outcomes in populations.     

Increased incidence of allergic rhinitis,bronchitis and asthma,in children living near a petrochemical complex with SO2 pollution

This study aims to investigate incidence of allergic rhinitis, bronchitis and asthma, in children living near a petrochemical complex with SO₂ pollution obtained by air monitoring stations. A total of 587 children aged 11 to 14 were recruited and classified into high and low exposure groups based on a radius of 10 km from the complex. To study the influence of health on children since the operation of complex in 1999 and observe the difference of these diseases' short-term and long-term impact, we obtained the incidence rates of allergic rhinitis (ICD-9: 477), bronchitis (490–491) and asthma (493) from the Taiwan Health Insurance Database for three periods: 1999–2002, 1999–2006, and 1999–2010. Since 2001, the mean and 99th percentile of SO₂ concentrations in the high exposure area have been significantly higher than those in low exposure area. There were significant differences between the high and low exposure groups in the percentage of smoking, alcohol consumption, passive smoking exposure and incense burning habits. The incidence rates of three intervals were 26.9%, 35.7%, 41.7%; 8.3%, 8.8%, 10.2%; 18.5%, 25.0%, 26.9% for allergic rhinitis, bronchitis and asthma in high exposure group. Significant differences were found between groups for allergic rhinitis in all periods, bronchitis in the first two periods, and asthma in the first period using Student's t-test. After we adjusted age, gender, group, living near roads, incense burning and passive smoking exposure, the hazard ratios between exposure groups were 3.05, 2.74, and 1.93 for allergic rhinitis with significant difference in three periods, and 2.53, 1.92 and 1.72 for bronchitis with significant difference in first period and 1.60, 1.28 and 1.29 for asthma with significant difference in first period by Cox regression. The higher incidence of allergic rhinitis was related to boys and living near roads and the higher incidence of asthma was also related to younger children, boys, and passive smoking exposure.     

Flame retardants in indoor dust and air of a hotel in Japan

Occurrence of flame retardants (FRs) in the indoor environment of highly flame-retarded public facilities is an important concern from the viewpoint of exposure because it is likely that FRs are used to a greater degree in these facilities than in homes. For this study, brominated flame-retardants (BFRs) and organophosphate flame-retardants and plasticizers (OPs), and brominated dibenzo-p-dioxins/furans (PBDD/DFs) were measured in eight floor dust samples taken from a Japanese commercial hotel that was assumed to have many flame-retardant materials. Concentrations of polybrominated diphenylethers (PBDEs) and hexabromocyclododecanes (HBCDs) varied by about two orders of magnitude, from 9.8–1700 ng/g (median of 1200 ng/g) and from 72–1300 ng/g (median of 740 ng/g), respectively. Concentrations of the two types of BFRs described above were most dominant among the investigated BFRs in the dust samples. It is inferred that BFR and PBDD/DF concentrations are on the same level as those in house and office dust samples reported based on past studies. Regarding concentrations of 11 OPs, 7 OPs were detected on the order of micrograms per gram, which are equivalent to or exceed the BFR concentrations such as PBDEs and HBCDs. Concentrations of the investigated compounds were not uniform among dust samples collected throughout the hotel: concentrations differed among floors, suggesting that localization of source products is associated with FR concentrations in dust. Passive air sampling was also conducted to monitor BFRs in the indoor air of hotel rooms: the performance of an air cleaner placed in the room was evaluated in terms of reducing airborne BFR concentrations. Monitoring results suggest that operation of an appropriate air cleaner can reduce both gaseous and particulate BFRs in indoor air.     

Bacillus thuringiensis, nucleopolyhedrosis virus,and pheromones: Environmental considerations and uncertainties in large-scale insect control

The mode of action, extent of use, and the current knowledge on environmental fate and toxicity of three biological insecticides [Bacillus thuringiensis (B.t.), nucleopolyhedrosis virus (NPV), and pheromones] are reviewed. Data gaps, environmental uncertainties in any large-scale use, and proposed registration guidelines which may lead to more extensive use are discussed. B.t. disappears rapidly from plant foliage on exposure to sunlight and/or moisture, although it may persist in dry soil for several months or years. Foliar-applied NPVs are also inactivated by sunlight; the halflife on cotton leaves is 20–25 h. In the soil, NPVs may remain active for several years. Pheromones volatilize readily and do not persist in plant or in soil. Limited available data indicate that B.t. and pheromones do not persist in aquatic environments; quantitative data are unavailable for NPVs. Based on bioassay data, the three insecticides exhibit undetectable to low toxicity to nontarget organisms; there are also no reports of human disease or injury due to exposure to these pesticides and no bioaccumulation is expected with normal application. Except for B.t. which has been used in a limited large-scale applications, pest control uses of NPVs and pheromones are still in experimental stages. Areas of uncertainties requiring research and development include potential adverse health and ecological impacts in any large-scale and widespread use and efficacy and cost relative to synthetic chemical pesticides.     

Neurobehavioral performance in adolescents is inversely associated with traffic exposure

On the basis of animal research and epidemiological studies in children and elderly there is a growing concern that traffic exposure may affect the brain. The aim of our study was to investigate the association between traffic exposure and neurobehavioral performance in adolescents. We examined 606 adolescents. To model the exposure, we constructed a traffic exposure factor based on a biomarker of benzene (urinary trans,trans-muconic acid) and the amount of contact with traffic preceding the neurobehavioral examination (using distance-weighted traffic density and time spent in traffic). We used a Bayesian structural equation model to investigate the association between traffic exposure and three neurobehavioral domains: sustained attention, short-term memory, and manual motor speed. A one standard deviation increase in traffic exposure was associated with a 0.26 standard deviation decrease in sustained attention (95% credible interval: − 0.02 to − 0.51), adjusting for gender, age, smoking, passive smoking, level of education of the mother, socioeconomic status, time of the day, and day of the week. The associations between traffic exposure and the other neurobehavioral domains studied had the same direction but did not reach the level of statistical significance. The results remained consistent in the sensitivity analysis excluding smokers and passive smokers. The inverse association between sustained attention and traffic exposure was independent of the blood lead level. Our study in adolescents supports the recent findings in children and elderly suggesting that traffic exposure adversely affects the neurobehavioral function.     

Nonylphenol and octylphenol in human breast milk

Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 mug/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 mug/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.     

Prenatal and postnatal insecticide use and infant neuropsychological development in a multicenter birth cohort study

There is little evidence about exposure to currently used insecticides during early life periods and adverse effects on child neuropsychological development. The aim of this study is to examine the association between residential insecticide use during pregnancy and infancy, and the development of children.Study subjects were participants in the INMA (Environment and Childhood) Project, a Spanish multicenter birth cohort study. Prenatal and postnatal use of indoor insecticides and other variables were obtained from personal interview during pregnancy and infancy. Mental and psychomotor development was assessed around 14 months using the Bayley Scales of Infant Development. The associations were analyzed by linear regression models.54% of women used indoor insecticides at home during pregnancy and 47% postnatally. 34% of women used insecticide sprays and 33% used plug-in devices during pregnancy. During infancy, the percentage of women who used insecticide sprays decreased (22%), but the use of plug-in devices was similar to the prenatal period (32%). The use of insecticide sprays during pregnancy was associated with a decrement in psychomotor development (β = − 1.9; 95%CI: − 3.4, − 0.5) but postnatal use did not associate with mental and psychomotor development. The negative effect was enhanced according to some modifying factors, such as being female, higher levels of prenatal exposure to PCB and mercury and belonging to the lowest social class.We found certain evidence about the adverse effect of using insecticide sprays during pregnancy on the psychomotor development of children. Some socio-demographic factors and other exposures could enhance that effect.     

Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother–child cohort

Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment.The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders.Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend = 0.04 and P-trend < 0.01, respectively) and with working memory scores (P-trend = 0.05 and P-trend < 0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA).Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6 years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance.     

Effects of prenatal exposure to perfluoroalkyl acids on prevalence ofallergic diseases among 4-year-old children

Perfluoroalkyl acids (PFAAs) are ubiquitous chemicals extremely resistant and widespread throughout the environment, frequently being detected in human blood samples. Animal studies have revealed that exposure to PFAAs results in immunotoxicity. However, the association between PFAAs, especially long-chain PFAAs, and allergies in humans is not well established. We examined whether prenatal exposure to PFAAs is associated with allergic diseases among 4-year-old children in a large-scale prospective birth cohort in Hokkaido, Japan. In total, 1558 mother–child pairs were included in this study and prenatal levels of eleven PFAAs were measured in maternal plasma samples obtained between 28 and 32 weeks of pregnancy by using ultra-performance liquid chromatography-tandem mass spectrometry. Participant demographic and characteristic information were obtained from self-administered pre- and postnatal questionnaires and medical birth records. Infant allergies were assessed using the Japanese version of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three questionnaire, which was administered 4 years post-delivery. Symptoms included eczema, wheezing and rhinoconjunctivitis with a prevalence of 19.0%, 18.7%, and 5.4%, respectively. Associations of PFAA quartiles with allergic outcomes were examined using logistic models. Adjusted odds ratios (ORs) in the 4th quartile vs. 1st quartile (Q4 vs. Q1) for total allergic diseases (including at least one allergic outcome) significantly decreased for perfluorododecanoic acid (PFDoDa) (Q4 vs. Q1 OR: 0.621; 95% confidence interval (CI): 0.454, 0.847) and perfluorotridecanoic acid (PFTrDA) (Q4 vs. Q1 OR: 0.712; 95% CI: 0.524, 0.966) in all children. We obtained similar results when examining the association between PFAAs and eczema. The adjusted OR (Q4 vs. Q1) for wheezing in relation to higher maternal PFHxS levels was 0.728 (95% CI: 0.497, 1.06) in all children. In conclusion, prenatal exposure to long-chain PFAAs, such as PFDoDa and PFTrDA may have an immunosuppressive effect on allergic diseases in 4-year-old children.     

Linking empirical estimates of body burden of environmental chemicals and wellness using NHANES data

Biomonitoring of industrial chemicals in human tissues and fluids has shown that all people carry a “body burden” of synthetic chemicals. Although measurement of an environmental chemical in a person's tissues/fluids is an indication of exposure, it does not necessarily mean the exposure concentration is sufficient to cause an adverse effect. Since humans are exposed to multiple chemicals, there may be a combination effect (e.g., additive, synergistic) associated with low-level exposures to multiple classes of contaminants, which may impact a variety of organ systems. The objective of this research is to link measures of body burden of environmental chemicals and a “holistic” measure of wellness. The approach is demonstrated using biomonitoring data from the National Health and Nutrition Examination Surveys (NHANES). Forty-two chemicals were selected for analysis based on their detection levels. Six biological pathway-specific indices were evaluated using groups of chemicals associated with each pathway. Five of the six pathways were negatively associated with wellness. Three non-zero interaction terms were detected which may provide empirical evidence of crosstalk across pathways. The approach identified five of the 42 chemicals from a variety of classes (metals, pesticides, furans, polycyclic aromatic hydrocarbons) as accounting for 71% of the weight linking body burden to wellness. Significant interactions were detected indicating the effect of smoking is exacerbated by body burden of environmental chemicals. Use of a holistic index on both sides of the exposure-health equation is a novel and promising empirical “systems biology” approach to risk evaluation of complex environmental exposures.     

Particle size: A missing factor in risk assessment of human exposure to toxic chemicals in settled indoor dust

For researches on toxic chemicals in settled indoor dust, selection of dust fraction is a critical influencing factor to the accuracy of human exposure risk assessment results. However, analysis of the selection of dust fraction in recent studies revealed that there is no consensus. This study classified and presented researches on distribution of toxic chemicals according to dust particle size and on relationship between dust particle size and human exposure possibility. According to the literature, beyond the fact that there were no consistent conclusions on particle size distribution of adherent fraction, dust with particle size less than 100 μm should be paid more attention and that larger than 250 μm is neither adherent nor proper for human exposure risk assessment. Calculation results based on literature data show that with different selections of dust fractions, analytical results of toxic chemicals would vary up to 10-fold, which means that selecting dust fractions arbitrarily will lead to large errors in risk assessment of human exposure to toxic chemicals in settled dust. Taking into account the influence of dust particle size on risk assessment of human exposure to toxic chemicals, a new methodology for risk assessment of human exposure to toxic chemicals in settled indoor dust is proposed and human exposure parameter systems to settled indoor dust are advised to be established at national and regional scales all over the world.     

Retrospective exposure assessment in a chemical research and development facility

The objective of this exposure assessment was to reconstruct cumulative historical exposures for workers who have been exposed to multiple chemicals and chemical groups to better understand a cluster of brain cancers within a research and development lab. Chemicals of interest, including acrylates, bis-chloromethyl ether (BCME), chloromethyl methyl ether (CMME), isothiazolones and nitrosoamines, were selected on the basis of the plausibility of penetrating the blood-brain barrier and the uniqueness of the chemical's biological activity.In a complicated exposure setting such as a chemical R&D facility, multiple exposure estimation methods were needed. First, similarly exposure groups (SEGs) were created for these materials based on department group, time period of the department's existence and function associated with job titles. A probabilistic framework for assessing exposures was developed using Bayesian analysis of historical monitoring data, mathematical exposure modeling and professional judgments of current and former industrial hygienists at the facility were used to reconstruct the exposure history for acrylates, BCME and CMME for each SEG over the time period of interest. Since sufficient measurement data for isothiazolones and nitrosoamines were not available, the exposure histories for each SEG for these chemicals were estimated. This was done using objective formaldehyde levels and subjective employee interviews. The interviews assessed workplace determinants of exposure as distinct surrogates for estimating inhalation and dermal exposures. The exposure assessments by these methods were compared against each other to estimate the potential for exposure misclassification. A job exposure matrix (JEM) was constructed that contained the exposures obtained from above multiple approaches for each of these chemical groups for each SEG for each year of interest. The combination of methods used in this work is a unique and potentially helpful framework that can be used in analogous workplace settings involving multiple exposures with incomplete objective measurement information.