Proposed PCB congener groupings for epidemiological studies.

Polychlorinated biphenyls (PCBs) have been the target of many epidemiological studies because of their toxic potential and widespread prevalence in the environment. Advances in analytic techniques have made it possible to distinguish routinely among the 209 different congeners, which vary widely in their biological properties. We propose here a classification system for the most commonly detected congeners. Group 1 (potentially estrogenic, weak phenobarbital inducers); Group 2 (potentially antiestrogenic and immunotoxic, dioxinlike); and Group 3 (phenobarbital, CYP1A and CYP2B inducers, biologically persistent). Group 2 is further subdivided according to non- and mono-ortho substituted vs. di-ortho substituted, in analogy with toxicity of dioxin congeners

Prenatal Insecticide Exposures and Birth Weight and Length among an Urban Minority Cohort

We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother–newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), −81.8 to −3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, −0.47 to −0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, −375.2 to −45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p ≤ 0.007) among newborns born before the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides

International Studies of Prenatal Exposure to Polycyclic Aromatic Hydrocarbons and Fetal Growth

OBJECTIVES: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed human mutagens and carcinogens. However, lack of adequate air monitoring data has limited understanding of the effects of airborne PAHs on fetal growth. To address this gap in knowledge, we examined the association between prenatal exposure to airborne PAHs and birth weight, birth length, and birth head circumference, respectively, in Krakow, Poland, and New York City (NYC). METHODS: The parallel prospective cohort studies enrolled nonsmoking, healthy, and nonoccupationally exposed women and their newborns. Personal air monitoring of pregnant women was conducted over 48 hr. To control for maternal environmental tobacco smoke (ETS) exposure, we excluded those with umbilical cord plasma cotinine concentrations > 25 ng/mL. Mean cord plasma cotinine concentrations in both ethnic groups were ≤ 0.5 ng/mL. RESULTS: Prenatal PAH exposure was 10-fold higher in Krakow than in NYC. Prenatal PAH exposure was associated with significantly reduced birth weight in both Krakow Caucasians (p < 0.01) and in NYC African Americans (p < 0.01), controlling for known and potential confounders, but not in NYC Dominicans. Within the lower exposure range common to the two cities (1.80–36.47 ng/m(3)), the effect per unit PAH exposure on birth weight was 6-fold greater for NYC African Americans than for Krakow Caucasians (p = 0.01). CONCLUSIONS: These results confirm the adverse reproductive effect of relatively low PAH concentrations in two populations and suggest increased susceptibility of NYC African Americans. Fetal growth impairment has been linked to child developmental and health problems. Thus, substantial health benefits would result from global reduction of PAH emissions

Assessment of Benzo(a)pyrene-equivalent Carcinogenicity and Mutagenicity of Residential Indoor versus Outdoor Polycyclic Aromatic Hydrocarbons Exposing Young Children in New York City

The application of benzo(a)pyrene (BaP)-toxic equivalent factor to polycyclic aromatic hydrocarbons (PAH) concentrations can provide a more accurate risk assessment from environmental exposure to PAH. We hypothesized that BaP-equivalent toxicity determined following residential air monitoring among young urban children may vary by season. Residential indoor and outdoor air levels of PAH measured over two-weeks in a cohort of 5–6 year old children (n = 260) in New York City were normalized to the cancer and mutagen potency equivalent factor of BaP (BaP = 1). Data are presented as carcinogenic equivalents (BaP-TEQ) and mutagenic equivalents (BaP-MEQ) for the sum of 8 PAH (∑8PAH; MW ³ 228) and individual PAH and compared across heating versus nonheating seasons. Results show that heating compared to nonheating season was associated significantly with higher (BaP-TEQ)∑8PAH and (BaP-MEQ)∑8PAH both indoors and outdoors (p less than 0.001). Outdoor (BaP-TEQ)∑8PAH and (BaP-MEQ)∑8PAH were significantly higher than the corresponding indoor measures during the heating season (p less than 0.01). These findings suggest that at levels encountered in New York City air, especially during the heating season, residential exposure to PAH may pose an increased risk of cancer and mutation

Validation and Calibration of a Model Used to Reconstruct Historical Exposure to Polycyclic Aromatic Hydrocarbons for Use in Epidemiologic Studies

OBJECTIVES: We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case–control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model. METHODS: Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects’ homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH–DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station. RESULTS: The data for soil, PAH–DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40–80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection

Epidemiologic Evaluation of Measurement Data in the Presence of Detection Limits

Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of “fill-in” values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5–10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case–control study of non-Hodgkin lymphoma