The East Bay Diesel Exposure Project: a biomonitoring study of parents and their children in heavily impacted communities.

BACKGROUND: Diesel exhaust (DE) exposures pose concerns for serious health effects, including asthma and lung cancer, in California communities burdened by multiple stressors. OBJECTIVE: To evaluate DE exposures in disproportionately impacted communities using biomonitoring and compare results for adults and children within and between families. METHODS: We recruited 40 families in the San Francisco East Bay area. Two metabolites of 1-nitropyrene (1-NP), a marker for DE exposures, were measured in urine samples from parent-child pairs. For 25 families, we collected single-day spot urine samples during two sampling rounds separated by an average of four months. For the 15 other families, we collected daily spot urine samples over four consecutive days during the two sampling rounds. We also measured 1-NP in household dust and indoor air. Associations between urinary metabolite levels and participant demographics, season, and 1-NP levels in dust and air were evaluated. RESULTS: At least one 1-NP metabolite was present in 96.6% of the urine samples. Detection frequencies for 1-NP in dust and indoor air were 97% and 74%, respectively. Results from random effect models indicated that levels of the 1-NP metabolite 6-hydroxy-1-nitropyrene (6-OHNP) were significantly higher in parents compared with their children (p-value = 0.005). Urinary 1-NP metabolite levels were generally higher during the fall and winter months. Within-subject variability was higher than between-subject variability (~60% of total variance versus ~40%, respectively), indicating high short-term temporal variability. IMPACT: Biomonitoring, coupled with air monitoring, improves understanding of hyperlocal air pollution impacts. Results from these studies will inform the design of effective exposure mitigation strategies in disproportionately affected communities.

Current-use flame retardants: Maternal exposure and neurodevelopment in children of the CHAMACOS cohort.

Flame retardants are commonly used in consumer products found in U.S. households. Restrictions on the use of polybrominated diphenyl ether flame retardants have resulted in increased use of replacement chemicals, including Firemaster 550® (FM 550®) and organophosphate flame retardants (PFRs): tris(1,3- dichloro-2-propyl) phosphate (TDCIPP); tris(chloropropyl) phosphate (TCIPP); tris(2-chloroethyl) phosphate (TCEP); and triphenyl phosphate (TPHP). Animal research suggests that PFRs may affect neurodevelopment through noncholinergic mechanisms similar to some organophosphate (OP) pesticides. Despite the widespread presence of these compounds in home environments, and their structural similarity to neurotoxic OP pesticides, understanding of human exposure and health effects of PFRs is limited. We measured four urinary PFR metabolites from pregnant women in the CHAMACOS birth cohort study (n = 310) and assessed neurodevelopment of their children at age 7. Metabolites of TDCIPP (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and TPHP (DPHP: diphenyl phosphate) were detected in >75% of urine samples, and isopropylphenyl phenyl phosphate (ip-PPP), a metabolite of one component of FM 550®, was detected in 72% of urine samples. We observed decreases of 2.9 points (95% Confidence Interval (CI): -6.3, 0.5) and 3.9 points (95% CI: -7.3,-0.5) in Full-Scale intelligence quotient and Working Memory, respectively, for each ten-fold increase in DPHP in adjusted regression models (n = 248). Decreases in Full-Scale IQ and Working Memory were greater in models of the molar sum of the PFR metabolites compared to the DPHP models. This is the first study to examine PFR and FM 550® exposures and potential neurodevelopmental outcomes in pregnant women and children. Additional research is warranted.

Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort).

Organophosphate flame retardants (PFRs), used in consumer products since the 1970s, persist in the environment. Restrictions on penta-polybrominated diphenyl ether (PBDE) flame retardants resulted in increased use of Firemaster® 550 (FM® 550), and the organophosphate triesters: tris(1,3- dichloro-2-propyl) phosphate (TDCIPP); tris(chloropropyl) phosphate (TCIPP); tris(2-chloroethyl) phosphate (TCEP); and triphenyl phosphate (TPHP). The objectives of this study were to (1) identify determinants of flame retardants (4 PFRs, PentaBDEs and FM® 550) in house dust, (2) measure urinary PFR metabolites in pregnant women, and (3) estimate health risks from PFR exposure. We measured flame retardants in house dust (n = 125) and metabolites in urine (n = 310) collected in 2000-2001 from Mexican American women participating in the CHAMACOS birth cohort study in California. We detected FM® 550 and PFRs, including two (TCEP and TDCIPP) known to the state of California to cause cancer, in most dust samples. The maximum TCEP and TDCIPP dust levels were among the highest ever reported although the median levels were generally lower compared to other U.S. cohorts. Metabolites of TDCIPP (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and TPHP (DPHP: diphenyl phosphate) were detected in 78% and 79% of prenatal urine samples, respectively. We found a weak but positive correlation between TPHP in dust and DPHP in 124 paired prenatal urine samples (Spearman rho = 0.17; p = 0.06). These results provide information on PFR exposure and risk in pregnant women from the early 2000's and are also valuable to assess trends in exposure and risk given changing fire safety regulations and concomitant changes in chemical flame retardant use.

Phthalate exposure and risk assessment in California child care facilities.

Approximately 13 million U.S. children less than 6 years old spend some time in early childhood education (ECE) facilities where they may be exposed to potentially harmful chemicals during critical periods of development. We measured five phthalate esters in indoor dust (n = 39) and indoor and outdoor air (n = 40 and 14, respectively) at ECE facilities in Northern California. Dust and airborne concentrations were used to perform a probabilistic health risk assessment to compare estimated exposures with risk levels established for chemicals causing reproductive toxicity and cancer under California's Proposition 65. Di(2-ethylhexyl) phthalate (DEHP) and butyl benzyl phthalate (BBzP) were the dominant phthalates present in floor dust (medians = 172.2 and 46.8 µg/g, respectively), and dibutyl phthalate (DBP), diethyl phthalate (DEP), and diisobutyl phthalate (DIBP) were the dominant phthalates in indoor air (medians = 0.52, 0.21, and 0.10 µg/m(3), respectively). The risk assessment results indicate that 82-89% of children in California ECE had DBP exposure estimates exceeding reproductive health benchmarks. Further, 8-11% of children less than 2 years old had DEHP exposure estimates exceeding cancer benchmarks. This is the largest study to measure phthalate exposure in U.S. ECE facilities and findings indicate wide phthalate contamination and potential risk to developing children.

Flame retardant exposures in California early childhood education environments.

Infants and young children spend as much as 50h per week in child care and preschool. Although approximately 13 million children, or 65% of all U.S. children, spend some time each day in early childhood education (ECE) facilities, little information is available about environmental exposures in these environments. We measured flame retardants in air and dust collected from 40 California ECE facilities between May 2010 and May 2011. Low levels of six polybrominated diphenyl ether (PBDE) congeners and four non-PBDE flame retardants were present in air, including two constituents of Firemaster 550 and two tris phosphate compounds [tris (2-chloroethyl) phosphate (TCEP) and tris (1,3-dichloroisopropyl) phosphate (TDCIPP)]. Tris phosphate, Firemaster 550 and PBDE compounds were detected in 100% of the dust samples. BDE47, BDE99, and BDE209 comprised the majority of the PBDE mass measured in dust. The median concentrations of TCEP (319 ng g(-1)) and TDCIPP (2265 ng g(-1)) were similar to or higher than any PBDE congener. Levels of TCEP and TDCIPP in dust were significantly higher in facilities with napping equipment made out of foam (Mann-Whitney p-values<0.05). Child BDE99 dose estimates exceeded the RfD in one facility for children<3 years old. In 51% of facilities, TDCIPP dose estimates for children<6 years old exceeded age-specific "No Significant Risk Levels (NSRLs)" based on California Proposition 65 guidelines for carcinogens. Given the overriding interest in providing safe and healthy environments for young children, additional research is needed to identify strategies to reduce indoor sources of flame retardant chemicals.

Factors associated with serum polybrominated diphenyl ether (PBDE) levels among school-age children in the CHAMACOS cohort.

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants historically used in textiles, furniture, and electronic products. Recent studies have documented widespread PBDE exposure to humans, with higher levels measured in children than adults. We analyzed 10 tri- to hepta-BDE congener levels in blood collected from 7-year old Mexican-American children living in an agriculture community in California (n = 272). The most frequently detected PBDE congeners in child serum were BDE-47, -99, -100, and -153, all of which were measured in >99% of the children. We used multiple linear regression models to examine associations between child total PBDE levels (ng/g lipid) and determinants of exposure. Factors positively associated with higher PBDE levels in the children were total PBDE levels in maternal serum during pregnancy, duration of exclusive breastfeeding, and having no safe places to play in their neighborhood. Child BMI was inversely associated with serum PBDE levels (regression p-values <0.05). Our findings confirm that exposure to the penta-BDE mixture is ongoing, and that Mexican-American children living in California may be experiencing higher PBDE exposure from their environment compared to children sampled from the general U.S. population. Additional research is needed to assess the health impacts of these exposures.

Determinants of serum polybrominated diphenyl ether (PBDE) levels among pregnant women in the CHAMACOS cohort.

We measured levels of 10 polybrominated diphenyl ether (PBDE) congeners in serum collected during pregnancy and at delivery from 416 pregnant, predominantly immigrant, women living in Monterey County, CA. The most frequently detected congeners were BDE-47, -99, -100, and -153, all components of the penta mixture, detected in >97% of samples. We used multivariable regression models to examine factors associated with exposure to individual PBDE congeners as well as their total summed concentration (ng/g lipid). Prenatal and delivery total PBDE levels were correlated between sampling times (n = 21; Pearson r = 0.99, p < 0.001). In multivariable models, total PBDE levels increased significantly with time residing in the U.S. (p < 0.001) and among women with ≥3 pieces of stuffed furniture in their homes (p < 0.05). Women's total PBDE levels increased 4.0% (95% CI = 2.8, 5.3) for each additional year residing in the U.S., after adjustment for prepregnancy BMI, weight gain during pregnancy, and SES. Having ≥3 pieces of stuffed furniture in the home was associated with a 26.8% (95% CI = 2.0, 57.5) increase in women's serum PBDE levels. Findings suggest PBDE indoor contamination in California homes is contributing to human exposures in a population of recent immigrants.

Comparison of current-use pesticide and other toxicant urinary metabolite levels among pregnant women in the CHAMACOS cohort and NHANES.

BACKGROUND: We measured 34 metabolites of current-use pesticides and other precursor compounds in urine samples collected twice during pregnancy from 538 women living in the Salinas Valley of California, a highly agricultural area (1999-2001). Precursors of these metabolites included fungicides, carbamate, organochlorine, organophosphorus (OP), and pyrethroid insecticides, and triazine and chloroacetanilide herbicides. We also measured ethylenethiourea, a metabolite of the ethylene-bisdithiocarbamate fungicides. Repeat measurements of the compounds presented here have not been reported in pregnant women previously. To understand the impact of the women's regional environment on these findings, we compared metabolite concentrations from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) cohort with U.S. national reference data for 342 pregnant women sampled by the National Health and Nutrition Examination Survey (1999-2002). RESULTS: The eight metabolites detected in > 50% of samples [2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP); 1- and 2-naphthol; ortho-phenylphenol (ORTH); para-nitrophenol (PNP); 2,4,6-trichlorophenol (2,4,6-TCP); and 3,4,6-trichloro-2-pyridinol (TCPy)] may be related to home or agricultural pesticide use in the Salinas Valley, household products, and other sources of chlorinated phenols. More than 78% of women in this study had detectable levels of at least one of the OP pesticide-specific metabolites that we measured, and > 30% had two or more. The 95th percentile values of six of the most commonly detected (> 50%) compounds were significantly higher among the CHAMACOS women after controlling for age, race, socioeconomic status, and smoking [(2,4-DCP; 2,5-DCP; ORTH; PNP; 2,4,6-TCP; and TCPy); quantile regression p < 0.05]. CONCLUSIONS: Findings suggest that the CHAMACOS cohort has an additional burden of precursor pesticide exposure compared with the national sample, possibly from living and/or working in an agricultural area.

Pesticides in dust from homes in an agricultural area.

We collected indoor dust samples from homes in the Salinas Valley of California. Of 22 pesticides measured in 504 samples, permethrins and the organophosphate chlorpyrifos were present in highest amounts. In multivariate Tobit regression models among samples from 197 separate residences, reported agricultural uses of chlorpyrifos, a herbicide (2,3,5,6-tetrachloroterephthalate (DCPA)), and a fungicide (iprodione) on agricultural fields were significantly (p < 0.01) associated, with 83%, 19%, and 49% increases, respectively, in dust concentrations for each kg applied per day, near participant homes, in the month or season prior to sample collection. However, agricultural use of diazinon, which was 2.2 times that of chlorpyrifos, and of permethrin were not significantly associated with dust levels. Other variables independently associated with dust levels included temperature and rainfall, farmworkers storing work shoes in the home, storing a diazinon product in the home, housing density, having a home less clean, and having an air conditioner. Permethrins, chlorpyrifos, DCPA, and iprodione have either a log octanol-water partition coefficient (K(ow)) greater than 4.0, a very low vapor pressure, or both. Health risk assessments for pesticides that have these properties may need to include evaluation of exposures to house dust.

Occupational behaviors and farmworkers' pesticide exposure: findings from a study in Monterey County, California.

BACKGROUND: We studied the relationship between behaviors promoted through the US Environmental Protection Agency Worker Protection Standard (WPS) and other programs and agricultural pesticide exposures in 73 strawberry fieldworkers employed in Monterey County, California. METHODS: Farmworkers' behaviors were assessed via self-report and organophosphorus (OP) pesticide exposure was measured using dimethyl alkylphosphate (DMAP) and malathion dicarboxylic acid (MDA) urinary metabolite levels. RESULTS: Wearing WPS-recommended clothing, wearing clean work clothes, and the combination of handwashing with soap and wearing gloves were associated with decreases in DMAP and MDA metabolite levels. Despite these protective behaviors, however, participants had significantly higher levels of exposure as compared with a national reference sample. CONCLUSIONS: Interventions that facilitate compliance with these behaviors may be effective in decreasing fieldworkers' pesticide exposures. However, further efforts are needed to reduce the exposure disparities experienced by farmworkers and decrease the potential for "take home" exposures to farmworkers' families.

Merging models and biomonitoring data to characterize sources and pathways of human exposure to organophosphorus pesticides in the Salinas Valley of California.

We characterize cumulative intakes of organophosphorus (OP) pesticides in an agricultural region of California by drawing on human biomonitoring data, California pesticide use reporting (PUR) data, and limited environmental samples together with outputs from the CalTOX multimedia, multipathway, source-to-dose model. The study population is the CHAMACOS cohort of almost 600 pregnant Latina women in the Salinas Valley region. We use model estimates of OP intake and urinary dialkylphosphate (DAP) metabolite excretion to develop premises about relative contributions from different exposure sources and pathways. We evaluate these premises by comparing the magnitude and variation of DAPs in the CHAMACOS cohort with those of the whole U.S. population using data from the National Health and Nutrition Examination Survey (NHANES). This comparison supports the premise that diet is the common and dominant exposure pathway in both populations. Biomarker comparisons and model results support the observation that, relative to NHANES, the CHAMACOS population has a statistically significant (p < 0.001) added intake of OP pesticides with low inter-individual variability. We attribute the magnitude and small variance of this intake to residential nondietary exposures from local agricultural OP uses. These results show that mass-balance models can estimate exposures for OP pesticides within the range measured by biological monitoring.

Pesticides and their metabolites in the homes and urine of farmworker children living in the Salinas Valley, CA.

In support of planning efforts for the National Children's Study, we conducted a study to test field methods for characterizing pesticide exposures to 20 farmworker children aged 5-27 months old living in the Salinas Valley of Monterey County, California. We tested methods for collecting house dust, indoor and outdoor air, dislodgeable residues from surfaces and toys, residues on clothing (sock and union suits), food, as well as spot and overnight diaper urine samples. We measured 29 common agricultural and home use pesticides in multiple exposure media samples. A subset of organophosphorus (OP), organochlorine (OC) and pyrethroid pesticides were measured in food. We also analyzed urine samples for OP pesticide metabolites. Finally, we administered four field-based exposure assessment instruments: a questionnaire; food diary; home inspection; and a self-administered child activity timeline. Pesticides were detected more frequently in house dust, surface wipes, and clothing than other media, with chlorpyrifos, diazinon, chlorthal-dimethyl, and cis- and trans-permethrin detected in 90% to 100% of samples. Levels of four of these five pesticides were positively correlated among the house dust, sock, and union suit samples (Spearman's rho=0.18-0.76). Pesticide loading on socks and union suits was higher for the group of 10 toddlers compared to the 10 younger crawling children. Several OP pesticides, as well as 4,4'-DDE, atrazine, and dieldrin were detected in the food samples. The child activity timeline, a novel, low-literacy instrument based on pictures, was successfully used by our participants. Future uses of these data include the development of pesticide exposure models and risk assessment.

Assessment of potential risk levels associated with U.S. Environmental Protection Agency reference values.

The U.S. Environmental Protection Agency (U.S. EPA) generally uses reference doses (RfDs) or reference concentrations (RfCs) to assess risks from exposure to toxic substances for noncancer health end points. RfDs and RfCs are supposed to represent lifetime inhalation or ingestion exposure with minimal appreciable risk, but they do not include information about the estimated risk from exposures equal to the RfD/RfC. We used results from benchmark dose modeling approaches recently adopted for use in developing RfDs/RfCs to estimate the risk levels associated with exposures at the RfD/RfC. We searched the U.S. EPA Integrated Risk Information System (IRIS) database and identified 11 chemicals with oral RfDs and 12 chemicals with inhalation RfCs that used benchmark dose modeling. For assessments with sufficient model information, we found that 16 of 21 (76%) of the dose-response models were linear or supralinear. We estimated the risk from exposures at the established RfDs and RfCs for these chemicals using a linear dose-response curve to characterize risk below the observed data. Risk estimates ranged from 1 in 10,000 to 5 in 1,000 for exposures at the RfDs, and from 1 in 10,000 to 3 in 1,000 for exposures at the RfCs. Risk estimates for exposures at the RfD/RfC values derived from sublinear dose-response curves ranged from 3 in 1,000,000,000 to 8 in 10,000. Twenty-four percent of reference values corresponded to estimated risk levels greater than 1 in 1,000; 10 of 14 assessments had points of departure greater than the no-observed-adverse-effect levels. For policy development regarding management of cancer risks, the U.S. EPA often uses 1 in 1,000,000 as a de minimis risk level. Although noncancer outcomes may in some instances be reversible and considered less severe than cancer, our findings call into question the assumption that established RfD and RfC values represent negligibly small risk levels.