Trends in Urinary Metabolites of Polycyclic Aromatic Hydrocarbons (PAHs) in the Non-Smoking U.S. Population, NHANES 2001-2014

Abstract

Background:

Recent studies indicate airborne PAH levels have decreased in the U.S., but it is unclear if this has resulted in PAH exposure changes in the U.S. population.

Objective:

Examine temporal trends in urinary metabolites of Naphthalene, Fluorene, Phenanthrene, and Pyrene in U.S. non-smokers, 6+ years old.

Methods:

We used biomonitoring data from the National Health and Nutrition Examination Survey (NHANES) program, 2001-2014, (N=11,053) using survey weighted linear regression. Models were adjusted for age, sex, race/ethnicity, creatinine, BMI, income, diet, and seasonality. Stratified models evaluated the effect of age, sex, and race/ethnicity on trends.

Results:

Between 2001-2014, Naphthalene exposure increased 36% (p<0.01); Pyrene exposure increased 106% (p <0.01); Fluorene and Phenanthrene exposure decreased 55% (p <0.01), and 37% (p<0.01), respectively. Naphthalene was the most abundant urinary PAH, 20-fold higher than Fluorene and Phenanthrene, and over 50-fold higher than Pyrene compared to reference groups, effect modification was observed by age (Naphthalene, Pyrene), sex (Fluorene, Pyrene), and race/ethnicity (Naphthalene, Fluorene, Phenanthrene, Pyrene).

Significance:

This study shows exposure to Naphthalene and Pyrene increased, while exposure to Fluorene and Phenanthrene decreased among the non-smoking U.S. general population between 2001-2014, suggesting environmental sources of PAHs have changed over the time period.

Graphical Abstract

1. Introduction

Polycyclic aromatic hydrocarbons (PAHs) are organic compounds commonly found as complex mixtures in the environment (1). PAHs form by incomplete combustion of organic materials. This can be from natural events such as wildfires, and from anthropogenic activities, such as burning wood and fossil fuels (1), industrial processes (2), smoking (1), food preparation methods such as smoking and grilling (1), and waste incineration (1). PAH composition varies by source and environmental release conditions, such as temperature and oxygen level during combustion (1). PAHs enter the body through inhalation, ingestion, dermal absorption, and placental transfer (1). Once inside the body, PAHs are metabolized by the liver and excreted in urine and feces with an average half-life in the human body of <30-hours (3,4). Most PAHs excreted in urine are the more soluble hydroxylated metabolites, although some unmetabolized PAHs are also detectable (3). Due to the short PAH metabolite half-life and ability to be collected non-invasively, urinary samples are appropriate biomarkers of recent exposure and are often used for biomonitoring studies (5). Biomonitoring studies in the U.S. show that nearly 100% of the general population have detectable levels of urinary PAH metabolites (uPAHs) (5). The urinary metabolite of Pyrene, 1-hydroxypyrene, is often used as a surrogate urinary biomarker for all PAH exposure in human studies (6). While more cost-effective and time-efficient, only measuring 1-hydroxypyrene does not capture exposure to more prevalent PAHs, such as Naphthalene, which represents over 50% and 80% of the total airborne PAH concentration in indoor air (7) and outdoor air (8), respectively. Urinary biomarkers of exposure revealed Naphthalene as the dominant uPAH in the U.S. population in 2001-2002 (9).

There are hundreds of different types of PAHs and several pose human health risks including increased risk of cancer (10), cardiovascular disease (11,12), respiratory illness (13), reproductive hormone disruption (14), and adverse developmental effects (15,16). PAH toxicity and their widespread dispersion in the environment is a global health concern. In the U.S., public health surveillance actions and regulatory measures to monitor and control PAH exposure were initiated in the 1980s (2,17-19). These efforts have documented that air pollution is a major source of PAH exposure and that regulatory actions have had an effect in reducing airborne PAH concentrations. An ambient air monitoring study in the Great Lakes region from 1996-2003 by Sun, et al. (2006) reported that Fluorene, Phenanthrene, and Pyrene slightly decreased (20) since the implementation of Clean Air Act Amendments (1990) that included the adoption of Tier 1 vehicle emission standards, cleaner fuels, higher fuel efficiency, and more stringent diesel engine emissions (21). Another study by Liu et al. (2017) evaluated particle and gas-phase PAHs collected in ambient air by the U.S. Environmental Protection Agency (US EPA) from 1990-2014, and reported a general decreasing trend in PAH levels in ambient air except for Naphthalene, which increased between 1990-2002 (22). The authors showed traffic emissions were a major exposure source of Naphthalene in ambient air (22), an observation that was also reported by Lu, et al. (2005), who found over half the Naphthalene emissions in Southern California came from vehicle exhaust (23). In another air monitoring study, Narváez, et al. (2008) used data from personal air monitors and stationary air monitoring sites in New York City to evaluate trends in traffic pollutant exposure in non-smoking pregnant women and found that overall, airborne PAHs declined from 1998-2006 (24). The authors attributed the decrease in airborne PAH exposure to updates in the U.S. Clean Air Act (1970, as amended) requiring cleaner, lower emission diesel fuel, as well as local transit authority actions to increase the use of cleaner fuels in buses (24).

While these studies show evidence of decreasing PAH concentration in ambient air, it is unclear if these changes correspond to similar trends in the U.S. population. Therefore, we used National Health and Nutrition Examination Survey (NHANES) data to evaluate fourteen-years (2001-2014) of urinary Naphthalene, Fluorene, Phenanthrene and Pyrene metabolite concentrations among the non-smoking U.S. population. Our objective was to evaluate the trends in environmental PAH exposures at the population level by minimizing behavioral influences on these trends. Thus, we restricted our study to the non-smoking population because tobacco smoke contains high levels of PAHs. Additionally, we examined effect modification by age, sex, race/ethnicity, and reproductive age. Based on previous indoor and ambient air research (7,8,20,22,24,25), we hypothesized that uPAHs would decrease in the U.S. non-smoking population over this 14-year time period. We also hypothesized the trend in uPAH exposure would be lower in children compared to adults, lower in females compared to males overall and at reproductive age (18-49 years), and lower in Non-Hispanic Whites compared to other race/ethnicities.

2. Materials and Methods

2.1. Study Population

This analysis used seven NHANES cycles spanning 2001 to 2014. This publicly available data included 19,079 study participants aged 6+ years who were randomly selected to have their urine samples analyzed for uPAHs. NHANES is a complex, multi-stage survey design where the weighted sample is representative of the U.S. civilian non-institutionalized population (26). NHANES data are collected by the National Center for Health Statistics (NCHS), which is part of the U.S. Centers for Disease Control and Prevention (CDC). All participants provided informed consent and the NCHS research ethics review board approved the study protocols.

Of the 19,079 participants eligible to provide urine samples, 782 were excluded because of missing uPAH data, 3 were excluded for missing urinary creatinine data, and 315 were excluded because they were diagnosed with weak or failing kidneys, or had undergone dialysis in the past year. Of the remaining 17,979 participants, 2,918 were excluded for missing: serum cotinine data (n=1,382); individual or family PIR data (n=1,267); and BMI data (n=505). There were 236 participants who had missing data for more than one of these covariates. Of the remaining 15,061 participants, 4,008 did not meet the inclusion criterion of being a non-smoker as determined by serum cotinine levels ≤1 ng/mL, leaving a final analytical sample size of 11,053 participants.

2.2. Exposure Assessment

Eight uPAH metabolites were included in this analysis and grouped by parent PAH (5) to create four uPAH measurements: Naphthalene (1- and 2-hydroxynaphthalene, uNAP); Fluorene (2- and 3-hydroxyfluorene, uFLU); Phenanthrene (1-, 2- and 3-hydroxyphenanthrene, uPHEN); and Pyrene (1-hydroxypyrene, uPYR). Sample collection and analysis are described in detail elsewhere (26). Briefly, a spot urinary specimen was collected from participants at a Mobile Exam Center (MEC), stored at −20°C, then shipped to a CDC laboratory for analysis. The sample underwent enzymatic hydrolysis and solid-phase extraction, and analyzed using isotope dilution capillary gas chromatography combined with mass spectrometry (26). The percentage of uPAH metabolite samples above the analytical limit of detection (LOD) was >96% with the exception of uPYR in NHANES cycle 2013-14, in which 71% of samples were above the LOD. Since the LOD for uPAH metabolites changed across NHANES cycles, we followed the method applied by the CDC and assigned a value equivalent to the maximal LOD for each uPAH divided by the square root of two (17) for any uPAH below its respective LOD for uPAH metabolite data from NHANES cycles 2003-04 through 2013-14. We did not apply a maximal LOD imputation to uPAH metabolite data for the 2001-02 NHANES cycle as information regarding observations at/above or below the LOD was not publicly available. The LOD of each PAH metabolite, published in the Laboratory Procedure Manual for each NHANES cycle (27), is provided in Table S2 of the Supplementary Information.

Urinary creatinine was measured by clinical analyzer (26). The specified instrumentation for measuring creatinine changed within the sampling frame, but the LOD remained constant at 1 mg/mL, except for the 2013-2014 cycle when the LOD was lowered to 0.10 mg/dL (26). We assigned the maximal LOD of 1 mg/ml for creatinine divided by the square root of two for samples below the LOD. Urinary creatinine was used as a separate, independent variable in regression analysis to adjust for urinary dilution (28).

2.3. Covariates

We conducted a literature review to identify potential confounders and covariates that were associated with uPAH exposure. These include smoking, age, sex, race/ethnicity, diet, BMI, household income, time of year NHANES exam occurred (i.e., seasonality), work characteristics, and housing characteristics. To examine changes in environmental PAH exposure over time that are independent of changes in behavioral exposures, our sample population inclusion criteria selected non-smokers, as determined by serum cotinine levels ≤ 1 ng/mL. Serum cotinine is a biomarker of tobacco smoke exposure and has a longer half-life (15–20 hours), compared to nicotine (0.5–3 hours) (29). Detection and quantification methods for serum cotinine are described elsewhere (26). The LOD for serum cotinine was 0.5 ng/mL across NHANES cycles of interest (26). Observations below the LOD had been imputed by the CDC as the LOD divided by the square root of two. We adjusted for income and dietary sources of PAHs, and included covariates that can affect metabolism (age, sex, race/ethnicity, and BMI). We also used urinary creatinine concentration to adjust for urinary dilution, and adjusted for the time of year when participants took part in the NHANES medical exam.

Age in years was recoded as a categorical variable following guidance from NCHS for age group cutoffs (30). We created five age categories: 6-17 years, 18-29 years, 30-49 years, 50-64 years, and 65+ years. To investigate the trend difference between children and adults, age was also recoded as a dichotomous variable, with children age 6-17 years, and adults age 18+ years. Sex was a binary variable (male and female). Race/ethnicity groups were recoded as Non-Hispanic White, Mexican American, Non-Hispanic Black, and Other Hispanic/Other/Asian/Multi-Racial.

The amount of PAHs in foods can be affected by cooking or food processing methods (31). The NHANES 24-hour dietary recall data, and individual food code and description files, were used to create a dietary PAH variable in which foods expected to be high in PAHs and consumed by each participant were identified, using a list of keywords such as “grilled”, “smoked” or “cured” (Table S1 in the Supplemental Information). Participants were categorized as either having consumed, or not consumed food expected to be high in PAHs.

Body mass index (BMI) was included as a covariate because PAH exposure is associated with childhood obesity (32,33). BMI was categorized for children and teens using CDC established percentile ranges based on growth charts for age and sex (34). Adult BMI was calculated as the ratio of weight in kilograms by height in meters squared, and using the cut-off values specified by the CDC (35). For this study, child BMI for age percentiles were categorized as less than 85th percentile for “normal weight” (which included underweight due to small sample sizes), 85th-94th percentile for “overweight” and 95th or higher percentile for “obese.” Adults were categorized using the BMI cut-off values of less than 25 for “normal weight”, 25 to less than 30 for “overweight”; and ≥ 30 for “obese”.

Household income was characterized using the poverty-to-income ratio (PIR). PIR is calculated by dividing annual household income by the poverty threshold for family size in the state of residence within a given year, based on federal guidelines (26). For this study, PIR was recoded to a dichotomous variable, PIR < 2.00; PIR ≥ 2.00.

Seasonal fluctuations of airborne PAH compounds were expected because PAHs are more prevalent in ambient air during months when home heating is needed (22,36). The NHANES data includes a variable designating a six-month window when a participant took part in the medical exam. This information was used to create a seasonality variable: November 1^st through April 30^th, and May 1^st through October 31^st.

2.4. Statistical Analysis

Survey design factors including sample weights, pseudo strata, and pseudo sampling units, were applied according to NHANES analytical guidelines (30). Natural log-transformation was applied to the right-skewed uPAH and creatinine data. Survey weighted multiple linear regression models were constructed with each natural log-transformed uPAH as the outcome and NHANES cycle as the predictor.

Each model was adjusted for urinary creatinine, age, sex, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality. Sensitivity analyses included adjustments for work and housing characteristics, respectively. Models were used to yield estimated survey weighted and adjusted geometric mean (aGM) and 95% confidence interval (95%CI) of uPAH metabolites grouped by parent compound for each NHANES cycle from 2001-2002 to 2013-2014, overall, and at the 25^th, 50^th, 75^th and 95^th percentile. Effect modification between NHANES cycle and: 1) age, 2) sex, 3) reproductive age (age 18-49 years), and 4) race/ethnicity was examined by including two-way interaction terms. Residual diagnostics were examined to assess the assumptions of multiple linear regression models. Data analysis was conducted in Stata, version 15.1 (StataCorp LLC, College Station, TX).

3. RESULTS

The sample population’s selected socio-demographic characteristics in each NHANES cycle, as well the characteristics of participants excluded from the final sample, are described in the Supplemental Information (Tables S3 and S4, respectively). The overall temporal trends in uPAH biomarkers adjusted for covariates are presented in Table 1. On average during 2001-2014, Naphthalene was the most abundant uPAH with a weighted aGM (95%CI) of 5.65 ug/L (5.55, 5.74). This was 20 times higher than Fluorene (0.29 ug/L; 0.29, 0.30), and Phenanthrene (0.29 ug/L; 0.28, 0.29), and 57 times higher than Pyrene (0.10 ug/L; 0.09, 0.10). The trends in uPAH biomarkers at the 25^th, 50^th, 75^th and 95^th percentiles are also in Table 1 and illustrated in Figure 1. The change in Pyrene concentrations between 2001-02 and 2013-14 are within the maximal LOD of 0.07 ug/L at the 25^th and 50^th percentile, indicating that there is no meaningful change in Pyrene exposure over this time period amongst the participants whose exposure is below the median.

Table 1.

Estimated weighted and adjusted^(a) geometric mean (aGM) and 95% confidence interval (95%CI) of uPAH biomarkers (in ug/L),^(b) overall and by percentile, at each NHANES cycle. See Figure 1 for graphical representation.

	n	All NHANES Cycles	2001-02	2003-04	2005-06	2007-08	2009-10	2011-12	2013-14	p for trend(c)
uNAP
aGM overall	11,028	5.65 (5.55, 5.74)	4.19 (4.05, 4.33)	5.17 (4.94, 5.40)	5.89 (5.61, 6.17)	6.31 (6.07, 6.54)	5.93 (5.68, 6.17)	5.87 (5.59, 6.14)	6.04 (5.78, 6.30)	< 0.01
25th Pctl.	2,342	2.03 (1.99, 2.07)	2.43 (2.29, 2.57)	2.99 (2.73, 3.27)	3.52 (3.17, 3.91)	3.56 (3.28, 3.86)	3.29 (3.00, 3.61)	3.08 (2.81, 3.38)	3.08 (2.76, 3.42)	< 0.01
50th Pctl.	2,610	4.15 (4.11, 4.20)	3.96 (3.81, 4.11)	4.86 (4.58, 5.16)	5.42 (5.20, 5.66)	5.84 (5.60, 6.09)	5.45 (5.17, 5.74)	5.35 (4.99, 5.75)	5.28 (4.95, 5.63)	< 0.01
75th Pctl.	2,730	6.31 (6.26, 6.36)	5.51 (5.32, 5.71)	6.86 (6.60, 7.14)	7.59 (7.32, 7.88)	8.32 (7.94, 8.72)	7.93 (7.49, 8.40)	7.85 (7.50, 8.22)	8.12 (7.77, 8.49)	< 0.01
95th Pctl.	2,537	9.13 (9.04, 9.22)	8.23 (7.75, 8.74)	10.07 (9.62, 10.55)	11.77 (11.16, 12.41)	12.66 (11.87, 13.50)	12.30 (11.78, 12.83)	12.19 (11.61, 12.79)	13.24 (12.39, 14.16)	< 0.01
uFLU
aGM overall	10,989	0.29 (0.29, 0.30)	0.37 (0.36, 0.38)	0.30 (0.29, 0.32)	0.33 (0.31, 0.34)	0.32 (0.30, 0.33)	0.27 (0.26, 0.28)	0.27 (0.26, 0.28)	0.21 (0.20, 0.22)	< 0.01
25th Pctl.	2,527	0.11 (0.10, 0.11)	0.21 (0.020, 0.22)	0.17 (0.15, 0.19)	0.20 (0.18, 0.22)	0.18 (0.17, 0.20)	0.15 (0.14, 0.16)	0.14 (0.13, 0.15)	0.11 (0.10, 0.12)	< 0.01
50th Pctl.	2,675	0.22 (0.22, 0.22)	0.35 (0.34, 0.37)	0.29 (0.27, 0.31)	0.30 (0.29, 0.32)	0.30 (0.28, 0.32)	0.25 (0.24, 0.26)	0.24 (0.23, 0.25)	0.19 (0.17, 0.20)	< 0.01
75th Pctl.	2,757	0.33 (0.33, .0.33)	0.49 (0.47, 0.52)	0.41 (0.39, 0.43)	0.43 (0.41, 0.44)	0.42 (0.40, 0.45)	0.37 (0.36, 0.39)	0.37 (0.35, 0.40)	0.29 (0.28, 0.30)	< 0.01
95th Pctl.	2,286	0.47 (0.47, 0.48)	0.73 (0.69, 0.77)	0.60 (0.56, 0.64)	0.65 (0.63, 0.68)	0.64 (0.61, 0.68)	0.58 (0.55, 0.62)	0.57 (0.54, 0.59)	0.47 (0.44, 0.51)	< 0.01
uPHEN
aGM overall	11,012	0.29 (0.28, 0.29)	0.32 (0.31, 0.34)	0.31 (0.30, 0.33)	0.32 (0.30, 0.33)	0.30 (0.29, 0.32)	0.28 (0.27, 0.29)	0.26 (0.25, 0.27)	0.22 (0.21, 0.23)	< 0.01
25th Pctl.	2,658	0.11 (0.11, 0.11)	0.19 (0.18, 0.19)	0.18 (0.16, 0.20)	0.19 (0.18, 0.21)	0.17 (0.16, 0.19)	0.16 (0.15, 0.17)	0.14 (0.13, 0.15)	0.11 (0.10, 0.12)	< 0.01
50th Pctl.	2,936	0.21 (0.21, 0.22)	0.31 (0.29, 0.33)	0.30 (0.28, 0.33)	0.30 (0.28, 0.32)	0.28 (0.26, 0.31)	0.26 (0.25, 0.27)	0.24 (0.23, 0.25)	0.19 (0.18, 0.20)	< 0.01
75th Pctl.	2,791	0.32 (0.32, 0.33)	0.43 (0.40, 0.45)	0.42 (0.40, 0.44)	0.41 (0.39, 0.43)	0.40 (0.38, 0.42)	0.38 (0.37, 0.39	0.36 (0.34, 0.38)	0.29 (0.28, 0.31)	< 0.01
95th Pctl.	2,024	0.45 (0.45, 0.46)	0.61 (0.58, 0.65)	0.59 (0.57, 0.61)	0.60 (0.57, 0.63)	0.61 (0.59, 0.64)	0.57 (0.53, 0.62)	0.53 (0.49, 0.57)	0.44 (0.41, 0.48)	< 0.01
uPYR
aGM overall	10,955	0.10 (0.09, 0.10)	0.04 (0.04, 0.05)	0.08 (0.07, 0.08)	0.09 (0.08, 0.09)	0.11 (0.11, 0.12)	0.12 (0.11, 0.12)	0.11 (0.10, 0.11)	0.13 (0.12, 0.13)	< 0.01
25th Pctl(d)	2,353	0.04 (0.04, 0.04)	0.03 (0.02, 0.03)	0.04 (0.04, 0.05)	0.05 (0.05, 0.06)	0.06 (0.06, 0.07)	0.07 (0.06, 0.070)	0.06 (0.06, 0.06)	0.07 (0.06, 0.07	< 0.01
50th Pctl.(d)	2,342	0.07 (0.07, 0.07)	0.04 (0.04, 0.04)	0.07 (0.07, 0.08)	0.08 (0.08, 0.08)	0.10 (0.10, 0.11)	0.10 (0.10, 0.11)	0.10 (0.09, 0.10)	0.11 (0.11, 0.12)	< 0.01
75th Pctl.(d)	2,839	0.10 (0.10, 0.11)	0.06 (0.06, .06)	0.10 (0.10, 0.11)	0.11 (0.11, 0.12)	0.15 (0.14, 0.16)	0.15 (0.15, 0.16)	0.14 (0.14, 0.15)	0.17 (0.16, 0.18)	< 0.01
95th Pctl.	2,579	0.16 (0.15, 0.16)	0.09 (0.09, 0.10)	0.16 (0.15, 0.16)	0.17 (0.7 0.18)	0.22 (0.21, 0.23)	0.25 (0.23, 0.27)	0.23 (0.21, 0.24)	0.29 (0.28, 0.31)	< 0.01

^(a)Linear regression for the log-transformed uPAH biomarker, after LOD correction, adjusted for natural log-transformed urinary creatinine, age, sex, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality.

^(b)uNAP; sum of urinary Naphthalene metabolites (1- & 2-naphthol). uFLU: sum of urinary Fluorene metabolites (2- & 3-fluorene). uPHEN: sum of urinary Phenanthrene metabolites (1-, 2- & 3-phenanthrene). UPYR: urinary Pyrene metabolites.

^(c)p-value of weighted and adjusted geometric mean of trend across NHANES cycles was assessed by the adjusted Wald test, α = 0.05.

^(d)The delta in trend values between 2001-02 and 2013-14 are within the maximal analytical error for urinary Pyrene metabolite (0.07 ug/L). See Table S2 for more information on uPAH metabolite limit of detection values.

Figure 1.

Trends in uPAHs (ug/L) in the U.S. non-smoking population, age 6+ years, by 25^th, 50^th 75^th and 95^th percentile, 2001-2014. Weighted aGM and 95% confidence interval (95%CI) for each NHANES cycle estimated from linear regression models adjusted for urinary creatinine, age, sex, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality. (A) uNAP: sum of urinary Naphthalene metabolites (1- & 2-naphthol); (B) uFLU: sum of urinary Fluorene metabolites (2- & 3-fluorene); (C) uPHEN: sum of urinary Phenanthrene metabolites (1-, 2- & 3-phenanthrene); (D) uPYR: urinary Pyrene metabolites. See Table 1 to view these results in tabular form.

^(‡) The delta in trend values between 2001-02 and 2013-14 for the 25^th and 50^th percentiles are within the maximal analytical error for urinary Pyrene metabolite (0.07 ug/L).

From 2001-02 to 2013-14, Naphthalene and Pyrene concentrations increased in the U.S. general non-smoking population, while Fluorene and Phenanthrene concentrations decreased over the same time period. The average trend in Naphthalene between 2001-02 and 2013-14, expressed as the absolute difference divided by the average, changed from an aGM of 4.19 ug/L (95%CI: 4.05, 4.33) to 6.04 ug/L (5.78, 6.30; p < 0.01), a 36% increase. Pyrene increased 106%, from an aGM of 0.04 ug/L (95% CI: 0.04, 0.05) to 0.13 ug/L (95% CI: 0.12, 0.13; p < 0.01). Fluorene decreased 55%, from an aGM of 0.37ug/L (95% CI: 0.36, 0.38) to 0.21 ug/L (95% CI: 0.20, 0.22; p < 0.01). Phenanthrene decreased 37%, from aGM of 0.32ug/L (95% CI: 0.31, 0.34) to 0.22 ug/L (95% CI: 0.21, 0.23; p < 0.01). Naphthalene and Pyrene had the largest percent change from the previous cycle in 2003-04, which were increases of 23% and 100%, respectively. The trends for Fluorene and Phenanthrene fluctuated between 2001-02 and 2011-12, but were lower after 2011-12and had the largest percent change from the previous cycle in 2013-14, with decreases of 22% and 15%, respectively.

When respective uPAHs were grouped by percentiles, the greatest increase over time was observed amongst the highest exposures. Specifically, from 2001-01 to 2013-14, urinary biomarkers of Naphthalene exposure increased by 18%, 28%, 42%, and 58% amongst the 25^th, 50^th, 75^th and 95^th percentiles, respectively. Whereas, the trend for Fluorene was a 42%, 57%, 61%, and 62% decrease from 2001-02 to 2013-14, among the 25^th, 50^th, 75^th and 95^th percentiles, respectively. For Phenanthrene, the trend was a 37%, 47%, 46% and 45% decrease from 2001-02 to 2013-14, among the 25^th, 50^th, 75^th and 95^th percentiles, respectively. For Pyrene, the trend was a 21%, 33%, 45% and 66% increase from 2001-02 to 2013-14, among the 25^th, 50^th, 75^th and 95^th percentiles, respectively.

The stratified analyses are presented in Figures 2-5, Figures S1-S3, and in Table 2A-2B.

Figure 2.

Trends in uPAH metabolites by race/ethnicity in U.S. non-smokers, age 6+ years, 2001-2014. Weighted aGM and 95% confidence interval (95%CI) for each NHANES cycle estimated from linear regression models adjusted for urinary creatinine, age, sex, BMI, dietary sources of PAHs, PIR, and seasonality; interaction term is NHANES cycle##race/ethnicity. (A) uNAP: sum of urinary Naphthalene metabolites (1- & 2-naphthol) (B) uFLU: sum of urinary Fluorene metabolites (2- & 3-fluorene) (C) uPHEN: sum of urinary Phenanthrene metabolites (1-, 2- & 3-phenanthrene) (D) uPYR: urinary Pyrene metabolite. MA: Mexican American; NHW: Non-Hispanic White; NHB: Non-Hispanic Black; Other/Multi: Other/Multi-Racial. See Table 2B for more information.

^(‡) The change in urinary pyrene concentrations between 2001-02 and 2013-14 for Non-Hispanic White and Other/Multi-Racial groups are within the maximal analytical error.

Figure 5.

Trends in uPAH metabolites for males and females at reproductive age (18-49 years), in U.S. non-smokers, 2001-2014. Estimated weighted aGM^(b) and 95%CI by NHANES cycle. Weighted aGM and 95% confidence interval (95%CI) for each NHANES cycle estimated from linear regression models adjusted for urinary creatinine, age, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality; interaction term is NHANES cycle##sex, age restricted to 18-49 years. (A) uNAP: sum of urinary Naphthalene metabolites (1- & 2-naphthol), n = 11,028. (B) uFLU: sum of urinary Fluorene metabolites (2- & 3-fluorene), n = 10,989. (C) uPHEN: sum of urinary Phenanthrene metabolites (1-, 2- & 3-phenanthrene), n = 11,012. (D) uPYR: urinary Pyrene metabolites, n = 10,955. See Table 2A for more information.

^(‡) The delta in trend values between 2001-02 and 2013-14 for the 25^th and 50^th percentiles are within the maximal analytical error for urinary Pyrene metabolite (0.07 ug/L).

Table 2A.

Estimated weighted aGM and 95%CI (Lower 95%CI: LCI; Upper 95%CI: UCI) of uPAHs^(a) at each NHANES cycle. Adjusted for covariates^(b), and stratified by 1) age, 2) sex, and 3) at reproductive age (18-49 years). See Figures 3, 4 and 5, respectively, for graphical representation.

	1. Stratified by Age							2. Stratified by Sex, 6+ years							3. Stratified by Reproductive Age (18-49 Years)
	Children, 6-17 years			Adults, 18+ years				Males			Females				Men			Women
	aGM	LCI	UCI	aGM	LCI	UCI	p (c)	aGM	LCI	UCI	aGM	LCI	UCI	p	aGM	LCI	UCI	aGM	LCI	UCI	P
uNAP, Overall							< 0.01							0.21							<0.01
2001-02	4.02	3.68	4.36	4.23	4.06	4.41		4.35	4.15	4.56	4.06	3.86	4.26		4.36	4.09	4.63	3.91	3.68	4.15
2003-04	4.94	4.60	5.27	5.22	4.90	5.54		5.40	5.00	5.80	4.98	4.74	5.21		5.64	5.04	6.24	4.93	4.67	5.20
2005-06	4.82	4.55	5.10	6.22	5.84	6.60		5.86	5.59	6.14	5.90	5.57	6.24		5.61	5.27	5.95	6.36	5.80	6.92
2007-08	5.51	5.15	5.87	6.50	6.19	6.81		6.52	6.24	6.80	6.14	5.85	6.43		7.13	6.52	7.74	5.73	5.37	6.10
2009-10	5.70	5.38	6.03	5.95	5.68	6.23		5.96	5.76	6.17	5.86	5.50	6.21		5.64	5.34	5.94	6.23	5.71	6.75
2011-12	5.85	5.43	6.27	5.84	5.52	6.15		5.89	5.58	6.20	5.78	5.26	6.30		5.91	5.39	6.44	6.28	5.43	7.13
2013-14	6.48	6.00	6.96	5.92	5.65	6.18		5.91	5.64	6.19	6.12	5.72	6.51		5.62	5.18	6.06	7.05	6.51	7.58
uNAP, 25th percentile							< 0.01							<0.01							<0.01
2001-02	2.31	1.97	2.69	2.39	2.22	2.57		2.77	2.44	3.14	2.20	1.96	2.46		3.03	2.64	3.48	2.09	1.75	2.49
2003-04	3.15	2.83	3.50	2.92	2.54	3.36		3.51	3.04	4.04	2.54	2.20	2.92		3.85	3.31	4.49	2.53	2.00	3.20
2005-06	2.94	2.69	3.22	3.72	3.27	4.23		3.76	3.44	4.11	3.30	2.90	3.76		3.61	2.98	4.38	3.98	3.25	4.87
2007-08	3.29	2.93	3.68	3.58	3.31	3.88		4.11	3.92	4.32	3.01	2.73	3.32		5.10	4.17	6.23	3.06	2.35	3.98
2009-10	3.33	2.97	3.74	3.24	2.93	3.58		3.80	3.43	4.21	2.86	2.70	3.02		3.75	3.05	4.61	2.97	2.57	3.44
2011-12	3.17	2.43	4.14	3.12	2.89	3.38		3.47	3.02	3.99	3.00	2.63	3.42		3.44	2.69	4.40	3.07	2.57	3.66
2013-14	3.28	2.90	3.71	3.08	2.77	3.43		3.12	2.82	3.45	3.04	2.64	3.51		3.01	2.46	3.67	3.42	2.93	3.99
uNAP, 50th percentile							< 0.01							<0.01							<0.01
2001-02	3.74	3.35	4.18	3.95	3.78	4.12		4.23	4.04	4.43	3.64	3.42	3.87		4.24	4.02	4.46	3.60	3.14	4.12
2003-04	4.76	4.45	5.10	4.92	4.57	5.30		5.04	4.60	5.52	4.76	4.41	5.13		5.02	4.36	5.78	4.83	4.21	5.54
2005-06	4.32	4.11	4.53	5.79	5.41	6.19		5.44	5.17	5.72	5.38	5.15	5.62		5.74	5.33	6.17	5.96	5.63	6.31
2007-08	5.00	4.55	5.50	6.20	5.81	6.63		6.16	5.80	6.55	5.56	5.20	5.95		6.89	6.30	7.52	5.37	5.02	5.74
2009-10	5.07	4.76	5.40	5.45	5.09	5.83		5.67	5.39	5.96	5.16	4.64	5.74		5.53	4.99	6.14	5.35	4.60	6.23
2011-12	5.46	4.66	6.40	5.40	5.00	5.83		5.78	5.31	6.30	4.98	4.49	5.51		5.56	4.65	6.65	4.88	3.91	6.07
2013-14	5.57	4.91	6.31	5.22	4.91	5.55		5.52	5.17	5.89	5.11	4.56	5.72		5.12	4.47	5.87	5.83	5.04	6.74
uNAP, 75th percentile							< 0.01							<0.01							<0.01
2001-02	5.31	4.94	5.70	5.55	5.32	5.78		5.63	5.30	5.99	5.42	5.13	5.73		5.69	5.22	6.21	5.10	4.82	5.40
2003-04	6.52	6.03	7.06	6.85	6.46	7.26		7.08	6.56	7.63	6.68	6.44	6.94		7.51	6.71	8.40	6.67	6.30	7.06
2005-06	6.06	5.67	6.48	8.07	7.66	8.50		7.49	7.27	7.71	7.70	7.21	8.21		7.23	6.85	7.63	8.28	7.81	8.77
2007-08	7.28	6.81	7.77	8.66	8.24	9.10		8.46	7.93	9.02	8.11	7.67	8.57		9.28	8.43	10.22	7.42	6.65	8.28
2009-10	7.58	7.04	8.16	8.01	7.44	8.63		7.81	7.50	8.13	8.13	7.30	9.05		7.40	6.95	7.88	8.93	8.23	9.70
2011-12	7.67	7.32	8.04	7.81	7.36	8.29		7.85	7.35	8.39	7.91	7.24	8.64		8.10	7.55	8.68	9.12	7.79	10.68
2013-14	9.04	8.47	9.64	7.96	7.60	8.33		7.94	7.51	8.40	8.37	7.81	8.97		7.28	6.46	8.20	9.54	8.76	10.40
uNAP, 95th percentile							< 0.01							<0.01							<0.01
2001-02	7.82	7.18	8.53	8.61	8.15	9.08		8.08	7.64	8.55	8.69	7.88	9.59		7.99	7.63	8.36	7.81	7.26	8.40
2003-04	9.55	8.88	10.28	10.30	9.55	11.11		10.36	9.70	11.06	9.96	9.34	10.61		10.64	9.14	12.38	9.58	8.70	10.55
2005-06	9.70	9.14	10.30	12.33	11.61	13.10		11.50	10.72	12.32	11.96	11.39	12.56		10.37	9.52	11.31	12.30	11.43	13.23
2007-08	11.24	9.91	12.75	12.91	12.12	13.76		12.00	10.76	13.39	13.25	12.38	14.19		11.65	11.16	12.16	11.97	10.82	13.25
2009-10	11.49	10.79	12.23	12.62	11.92	13.37		11.53	10.82	12.29	12.77	11.82	13.79		10.27	9.48	11.12	13.89	12.58	15.33
2011-12	12.39	11.19	13.73	12.25	11.67	12.86		11.32	10.66	12.02	12.90	12.06	13.81		10.79	9.87	11.81	14.24	13.21	15.35
2013-14	13.92	12.71	15.24	12.98	12.11	13.91		12.96	11.85	14.18	14.38	13.05	15.85		12.04	10.83	13.38	15.71	14.00	17.64
uFLU, Overall							0.38							<0.01							<0.01
2001-02	0.40	0.37	0.43	0.36	0.34	0.38		0.42	0.40	0.44	0.33	0.31	0.35		0.46	0.43	0.50	0.33	0.30	0.35
2003-04	0.35	0.33	0.37	0.29	0.27	0.31		0.34	0.32	0.37	0.27	0.26	0.28		0.37	0.32	0.41	0.28	0.26	0.30
2005-06	0.35	0.33	0.38	0.32	0.30	0.34		0.38	0.36	0.39	0.29	0.27	0.30		0.39	0.37	0.41	0.29	0.26	0.32
2007-08	0.35	0.33	0.37	0.31	0.29	0.32		0.36	0.34	0.37	0.28	0.27	0.30		0.40	0.37	0.43	0.29	0.27	0.31
2009-10	0.31	0.29	0.33	0.27	0.25	0.28		0.30	0.29	0.32	0.25	0.24	0.26		0.30	0.29	0.32	0.27	0.25	0.29
2011-12	0.30	0.28	0.32	0.26	0.25	0.28		0.31	0.29	0.33	0.24	0.22	0.25		0.33	0.30	0.36	0.25	0.22	0.29
2013-14	0.23	0.21	0.25	0.21	0.20	0.22		0.23	0.22	0.24	0.20	0.18	0.21		0.23	0.22	0.24	0.23	0.21	0.24
uFLU, 25th percentile							<0.01							<0.01							<0.01
2001-02	0.23	0.21	0.26	0.20	0.19	0.21		0.27	0.24	0.30	0.18	0.16	0.19		0.31	0.25	0.37	0.18	0.15	0.21
2003-04	0.22	0.20	0.24	0.15	0.13	0.18		0.23	0.19	0.26	0.14	0.12	0.16		0.26	0.22	0.31	0.14	0.12	0.18
2005-06	0.22	0.20	0.24	0.19	0.17	0.21		0.24	0.22	0.26	0.16	0.13	0.18		0.25	0.20	0.31	0.18	0.13	0.25
2007-08	0.20	0.19	0.22	0.17	0.15	0.19		0.23	0.21	0.25	0.14	0.12	0.16		0.27	0.23	0.31	0.16	0.13	0.20
2009-10	0.16	0.15	0.18	0.14	0.13	0.15		0.20	0.18	0.22	0.12	0.12	0.14		0.20	0.18	0.23	0.13	0.12	0.15
2011-12	0.14	0.11	0.19	0.14	0.13	0.15		0.17	0.15	0.20	0.12	0.11	0.13		0.19	0.14	0.25	0.12	0.10	0.14
2013-14	0.12	0.10	0.13	0.11	0.10	0.12		0.12	0.11	0.13	0.09	0.08	0.11		0.12	0.10	0.14	0.10	0.09	0.13
uFLU, 50th percentile							<0.01							<0.01							<0.01
2001-02	0.37	0.32	0.44	0.35	0.33	0.36		0.40	0.38	0.43	0.30	0.27	0.32		0.46	0.43	0.49	0.31	0.28	0.35
2003-04	0.33	0.31	0.36	0.27	0.25	0.30		0.32	0.30	0.36	0.26	0.24	0.28		0.34	0.29	0.40	0.27	0.23	0.31
2005-06	0.33	0.30	0.36	0.30	0.28	0.32		0.36	0.34	0.38	0.27	0.25	0.30		0.39	0.37	0.42	0.27	0.26	0.30
2007-08	0.32	0.30	0.35	0.30	0.28	0.31		0.34	0.33	0.36	0.26	0.23	0.29		0.39	0.35	0.43	0.28	0.26	0.30
2009-10	0.28	0.26	0.30	0.24	0.23	0.26		0.28	0.27	0.29	0.22	0.20	0.23		0.27	0.25	0.31	0.23	0.21	0.27
2011-12	0.27	0.23	0.31	0.24	0.23	0.25		0.29	0.26	0.32	0.20	0.18	0.23		0.32	0.27	0.37	0.20	0.16	0.25
2013-14	0.21	0.18	0.24	0.18	0.17	0.20		0.21	0.19	0.23	0.16	0.15	0.18		0.22	0.19	0.25	0.19	0.16	0.21
uFLU, 75th percentile							<0.01							<0.01							<0.01
2001-02	0.52	0.48	0.56	0.48	0.46	0.50		0.55	0.51	0.59	0.44	0.43	0.46		0.60	0.56	0.66	0.44	0.42	0.46
2003-04	0.46	0.43	0.49	0.40	0.37	0.43		0.44	0.41	0.48	0.37	0.35	0.39		0.48	0.42	0.55	0.38	0.35	0.41
2005-06	0.48	0.44	0.52	0.42	0.39	0.44		0.48	0.46	0.51	0.37	0.35	0.39		0.50	0.47	0.54	0.38	0.35	0.41
2007-08	0.44	0.41	0.48	0.42	0.39	0.45		0.46	0.44	0.48	0.38	0.37	0.40		0.52	0.47	0.57	0.39	0.36	0.42
2009-10	0.40	0.35	0.45	0.36	0.34	0.37		0.39	0.37	0.41	0.34	0.32	0.36		0.39	0.36	0.43	0.39	0.36	0.41
2011-12	0.41	0.38	0.43	0.36	0.34	0.39		0.41	0.39	0.43	0.32	0.30	0.35		0.45	0.41	0.48	0.37	0.32	0.42
2013-14	0.34	0.31	0.38	0.28	0.27	0.30		0.31	0.28	0.33	0.27	0.25	0.29		0.31	0.29	0.33	0.33	0.30	0.36
uFLU, 95th percentile							<0.01							<0.01							<0.01
2001-02	0.76	0.70	0.83	0.70	0.65	0.75		0.76	0.71	0.81	0.69	0.64	0.75		0.83	0.76	0.91	0.62	0.56	0.70
2003-04	0.67	0.63	0.71	0.57	0.52	0.62		0.66	0.62	0.70	0.53	0.50	0.56		0.68	0.58	0.81	0.55	0.53	0.58
2005-06	0.72	0.63	0.83	0.63	0.59	0.66		0.70	0.68	0.73	0.59	0.55	0.64		0.66	0.61	0.72	0.59	0.54	0.64
2007-08	0.68	0.60	0.77	0.62	0.58	0.67		0.65	0.60	0.70	0.62	0.57	0.67		0.69	0.60	0.79	0.62	0.55	0.70
2009-10	0.62	0.54	0.70	0.56	0.52	0.60		0.59	0.55	0.63	0.57	0.54	0.59		0.59	0.53	0.65	0.61	0.53	0.71
2011-12	0.62	0.57	0.66	0.56	0.53	0.59		0.62	0.56	0.68	0.53	0.49	0.58		0.60	0.53	0.69	0.59	0.53	0.65
2013-14	0.54	0.49	0.58	0.46	0.41	0.51		0.49	0.45	0.53	0.46	0.41	0.50		0.46	0.43	0.50	0.56	0.47	0.68
uPHEN, Overall							0.28							0.08							<0.01
2001-02	0.31	0.29	0.33	0.33	0.31	0.35		0.35	0.34	0.37	0.30	0.28	0.32		0.38	0.35	0.41	0.30	0.28	0.32
2003-04	0.33	0.31	0.35	0.31	0.29	0.33		0.34	0.31	0.36	0.29	0.28	0.31		0.37	0.32	0.41	0.30	0.27	0.33
2005-06	0.30	0.28	0.32	0.32	0.31	0.34		0.35	0.34	0.37	0.29	0.27	0.30		0.35	0.34	0.37	0.30	0.27	0.32
2007-08	0.30	0.28	0.32	0.30	0.29	0.32		0.33	0.31	0.35	0.28	0.26	0.29		0.36	0.33	0.39	0.29	0.27	0.31
2009-10	0.28	0.26	0.30	0.28	0.27	0.30		0.30	0.28	0.31	0.27	0.25	0.28		0.30	0.28	0.31	0.29	0.27	0.31
2011-12	0.25	0.23	0.27	0.26	0.25	0.28		0.29	0.26	0.31	0.24	0.22	0.25		0.30	0.27	0.33	0.26	0.23	0.29
2013-14	0.21	0.19	0.23	0.22	0.21	0.23		0.23	0.22	0.25	0.20	0.19	0.21		0.23	0.22	0.24	0.22	0.21	0.24
uPHEN, 25th percentile							<0.01							<0.01							<0.01
2001-02	0.19	0.17	0.21	0.19	0.17	0.20		0.23	0.21	0.25	0.17	0.15	0.18		0.24	0.20	0.29	0.16	0.14	0.19
2003-04	0.21	0.19	0.24	0.17	0.15	0.21		0.22	0.19	0.26	0.16	0.14	0.19		0.26	0.20	0.33	0.16	0.13	0.20
2005-06	0.18	0.17	0.20	0.20	0.18	0.22		0.23	0.21	0.25	0.17	0.14	0.20		0.23	0.19	0.27	0.20	0.16	0.24
2007-08	0.18	0.16	0.20	0.17	0.16	0.19		0.21	0.21	0.22	0.15	0.13	0.17		0.25	0.23	0.27	0.15	0.12	0.19
2009-10	0.15	0.14	0.17	0.16	0.15	0.18		0.19	0.17	0.21	0.14	0.13	0.15		0.21	0.18	0.24	0.14	0.12	0.16
2011-12	0.13	0.10	0.16	0.14	0.13	0.15		0.17	0.15	0.19	0.13	0.11	0.14		0.17	0.13	0.23	0.13	0.12	0.15
2013-14	0.11	0.10	0.13	0.11	0.10	0.13		0.13	0.12	0.13	0.10	0.09	0.12		0.11	0.10	0.13	0.10	0.09	0.12
uPHEN, 50th percentile							<0.01							<0.01							<0.01
2001-02	0.29	0.25	0.34	0.32	0.30	0.34		0.35	0.33	0.37	0.27	0.25	0.29		0.38	0.36	0.40	0.29	0.25	0.32
2003-04	0.32	0.30	0.34	0.30	0.27	0.33		0.32	0.29	0.36	0.27	0.25	0.30		0.36	0.31	0.41	0.29	0.26	0.33
2005-06	0.28	0.25	0.30	0.31	0.29	0.33		0.34	0.32	0.35	0.27	0.26	0.29		0.36	0.33	0.39	0.29	0.25	0.32
2007-08	0.29	0.26	0.31	0.29	0.27	0.32		0.32	0.30	0.34	0.25	0.23	0.27		0.35	0.32	0.39	0.28	0.25	0.32
2009-10	0.26	0.24	0.28	0.26	0.25	0.28		0.28	0.26	0.30	0.24	0.22	0.26		0.27	0.24	0.29	0.25	0.23	0.28
2011-12	0.23	0.20	0.26	0.24	0.23	0.26		0.27	0.25	0.30	0.21	0.18	0.24		0.28	0.24	0.32	0.22	0.18	0.26
2013-14	0.18	0.16	0.20	0.19	0.18	0.21		0.21	0.20	0.23	0.17	0.16	0.18		0.21	0.19	0.24	0.18	0.16	0.20
uPHEN, 75th percentile							<0.01							<0.01							<0.01
2001-02	0.41	0.39	0.44	0.43	0.41	0.45		0.46	0.42	0.49	0.40	0.38	0.43		0.48	0.43	0.54	0.40	0.37	0.43
2003-04	0.44	0.41	0.46	0.41	0.39	0.44		0.44	0.41	0.48	0.41	0.38	0.44		0.47	0.41	0.55	0.40	0.35	0.45
2005-06	0.38	0.35	0.41	0.42	0.41	0.43		0.46	0.44	0.48	0.38	0.37	0.40		0.46	0.44	0.48	0.38	0.36	0.41
2007-08	0.40	0.37	0.44	0.41	0.38	0.43		0.43	0.40	0.46	0.37	0.35	0.40		0.46	0.42	0.52	0.38	0.35	0.41
2009-10	0.38	0.34	0.42	0.38	0.36	0.40		0.39	0.37	0.42	0.37	0.35	0.39		0.39	0.36	0.42	0.40	0.38	0.43
2011-12	0.37	0.32	0.42	0.36	0.34	0.39		0.39	0.36	0.43	0.32	0.30	0.33		0.40	0.37	0.44	0.36	0.31	0.42
2013-14	0.30	0.25	0.34	0.29	0.27	0.31		0.31	0.29	0.33	0.28	0.25	0.30		0.31	0.28	0.34	0.32	0.28	0.36
uPHEN, 95th percentile							<0.01							<0.01							<0.01
2001-02	0.59	0.55	0.64	0.63	0.58	0.67		0.62	0.57	0.68	0.61	0.53	0.69		0.67	0.63	0.71	0.58	0.53	0.63
2003-04	0.63	0.58	0.69	0.59	0.57	0.61		0.60	0.56	0.65	0.59	0.55	0.62		0.64	0.55	0.75	0.64	0.59	0.68
2005-06	0.59	0.52	0.65	0.60	0.57	0.63		0.66	0.62	0.71	0.56	0.53	0.59		0.59	0.55	0.64	0.59	0.51	0.67
2007-08	0.64	0.56	0.73	0.60	0.57	0.64		0.63	0.60	0.66	0.60	0.55	0.65		0.66	0.57	0.76	0.61	0.53	0.69
2009-10	0.59	0.51	0.69	0.56	0.51	0.62		0.57	0.51	0.64	0.58	0.54	0.63		0.58	0.50	0.66	0.66	0.57	0.76
2011-12	0.53	0.48	0.60	0.53	0.49	0.57		0.53	0.45	0.61	0.50	0.46	0.55		0.56	0.49	0.63	0.58	0.52	0.66
2013-14	0.44	0.41	0.48	0.45	0.40	0.51		0.46	0.43	0.49	0.43	0.38	0.49		0.46	0.40	0.54	0.51	0.41	0.62
uPYR, Overall							<0.01							<0.01							<0.01
2001-02	0.06	0.05	0.06	0.04	0.04	0.04		0.05	0.05	0.05	0.04	0.04	0.04		0.05	0.05	0.06	0.04	0.04	0.04
2003-04	0.12	0.11	0.13	0.07	0.06	0.07		0.09	0.08	0.10	0.07	0.07	0.07		0.09	0.08	0.10	0.07	0.06	0.07
2005-06	0.12	0.11	0.12	0.08	0.07	0.08		0.10	0.09	0.10	0.08	0.08	0.09		0.10	0.09	0.10	0.09	0.08	0.10
2007-08	0.15	0.14	0.16	0.10	0.10	0.11		0.12	0.11	0.12	0.11	0.10	0.11		0.13	0.12	0.14	0.11	0.10	0.12
2009-10	0.16	0.15	0.17	0.10	0.10	0.11		0.12	0.11	0.12	0.11	0.11	0.12		0.12	0.12	0.13	0.13	0.12	0.14
2011-12	0.14	0.13	0.15	0.10	0.09	0.10		0.12	0.11	0.12	0.10	0.09	0.11		0.12	0.11	0.13	0.11	0.10	0.13
2013-14	0.16	0.15	0.17	0.12	0.12	0.13		0.13	0.12	0.13	0.13	0.12	0.14		0.13	0.12	0.13	0.14	0.13	0.15
uPYR, 25th percentile (d)							<0.01							<0.01							<0.01
2001-02	0.04	0.03	0.04	0.02	0.02	0.03	H	0.03	0.03	0.04	0.02	0.02	0.02		0.04	0.03	0.05	0.02	0.02	0.03
2003-04	0.08	0.08	0.09	0.04	0.03	0.04		0.06	0.05	0.07	0.04	0.03	0.04		0.07	0.05	0.08	0.04	0.03	0.04
2005-06	0.07	0.07	0.08	0.05	0.04	0.06		0.06	0.06	0.07	0.04	0.04	0.05		0.06	0.05	0.07	0.06	0.05	0.07
2007-08	0.10	0.09	0.11	0.06	0.05	0.07		0.08	0.07	0.08	0.05	0.05	0.06		0.10	0.09	0.11	0.06	0.05	0.08
2009-10	0.10	0.09	0.11	0.06	0.06	0.07		0.08	0.07	0.08	0.06	0.05	0.06		0.09	0.07	0.11	0.07	0.06	0.07
2011-12	0.08	0.06	0.10	0.06	0.05	0.06		0.07	0.06	0.08	0.05	0.05	0.06		0.07	0.06	0.09	0.06	0.05	0.07
2013-14	0.09	0.08	0.10	0.07	0.06	0.07		0.07	0.07	0.08	0.07	0.06	0.07		0.07	0.06	0.08	0.07	0.06	0.08
uPYR, 50th percentile (d)							<0.01							<0.01							<0.01
2001-02	0.06	0.05	0.06	0.04	0.04	0.04		0.05	0.05	0.05	0.04	0.03	0.04		0.05	0.05	0.06	0.04	0.04	0.04
2003-04	0.12	0.11	0.12	0.07	0.06	0.07		0.08	0.08	0.09	0.06	0.06	0.07		0.09	0.08	0.10	0.07	0.06	0.08
2005-06	0.11	0.10	0.12	0.07	0.07	0.08		0.09	0.09	0.09	0.07	0.07	0.08		0.09	0.09	0.10	0.08	0.07	0.09
2007-08	0.14	0.13	0.15	0.10	0.09	0.10		0.11	0.11	0.12	0.10	0.09	0.10		0.13	0.12	0.14	0.11	0.10	0.12
2009-10	0.15	0.14	0.16	0.10	0.09	0.10		0.11	0.10	0.12	0.10	0.09	0.11		0.11	0.11	0.12	0.11	0.10	0.13
2011-12	0.13	0.11	0.15	0.09	0.09	0.10		0.11	0.10	0.12	0.09	0.08	0.09		0.12	0.10	0.13	0.09	0.08	0.12
2013-14	0.14	0.12	0.16	0.11	0.10	0.12		0.12	0.11	0.12	0.11	0.10	0.12		0.12	0.11	0.13	0.12	0.11	0.14
uPYR, 75th percentile							<0.01							<0.01							<0.01
2001-02	0.08	0.07	0.08	0.05	0.05	0.06		0.06	0.06	0.07	0.05	0.05	0.06		0.07	0.06	0.07	0.05	0.05	0.06
2003-04	0.15	0.14	0.16	0.09	0.08	0.09		0.12	0.11	0.13	0.09	0.09	0.10		0.11	0.10	0.13	0.10	0.09	0.10
2005-06	0.15	0.14	0.16	0.10	0.10	0.11		0.13	0.12	0.13	0.11	0.10	0.11		0.12	0.12	0.12	0.11	0.10	0.13
2007-08	0.19	0.18	0.20	0.13	0.13	0.14		0.15	0.14	0.16	0.14	0.13	0.15		0.17	0.16	0.19	0.15	0.14	0.16
2009-10	0.22	0.20	0.24	0.14	0.13	0.14		0.15	0.15	0.16	0.15	0.14	0.16		0.16	0.15	0.17	0.18	0.17	0.19
2011-12	0.19	0.18	0.20	0.13	0.13	0.14		0.15	0.14	0.16	0.14	0.12	0.15		0.16	0.15	0.17	0.16	0.14	0.19
2013-14	0.22	0.20	0.24	0.16	0.15	0.17		0.17	0.16	0.18	0.17	0.16	0.18		0.17	0.15	0.18	0.20	0.18	0.22
uPYR, 95th percentile							<0.01							<0.01							<0.01
2001-02	0.11	0.10	0.12	0.08	0.07	0.09		0.10	0.09	0.10	0.09	0.08	0.09		0.09	0.08	0.10	0.08	0.07	0.09
2003-04	0.22	0.20	0.24	0.12	0.12	0.13		0.17	0.16	0.18	0.14	0.14	0.15		0.17	0.15	0.19	0.13	0.12	0.14
2005-06	0.22	0.19	0.24	0.14	0.14	0.15		0.18	0.16	0.19	0.17	0.16	0.18		0.16	0.14	0.18	0.17	0.15	0.19
2007-08	0.29	0.26	0.31	0.19	0.18	0.20		0.20	0.19	0.22	0.23	0.21	0.26		0.22	0.19	0.25	0.23	0.21	0.26
2009-10	0.32	0.30	0.35	0.20	0.19	0.21		0.23	0.21	0.26	0.26	0.24	0.29		0.23	0.20	0.25	0.28	0.25	0.31
2011-12	0.28	0.26	0.30	0.20	0.18	0.21		0.22	0.20	0.24	0.23	0.22	0.25		0.22	0.21	0.24	0.25	0.22	0.30
2013-14	0.33	0.31	0.36	0.25	0.23	0.27		0.27	0.25	0.30	0.32	0.29	0.35		0.25	0.23	0.27	0.33	0.27	0.41

^(a)uNAP; sum of urinary Naphthalene metabolites (ug/L). uFLU: sum of urinary Fluorene metabolites (ug/L). uPHEN: sum of urinary Phenanthrene metabolites (ug/L). UPYR: urinary Pyrene metabolites (ug/L).

^(b)Model for age: adjusted for urinary creatinine, sex, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality; interaction term is NHANES cycle##age. Model for sex 6+years: adjusted for urinary creatinine, age, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality; interaction term is NHANES cycle##sex. Model for sex at reproductive age: same as model for sex, but age restricted to 18-49 years.

^(c)p-value for the overall trend in weighted aGM between groups across NHANES cycles was assessed by the adjusted Wald test, α = 0.05.

^(d)The delta in trend values between 2001-02 and 2013-14 are within the maximal analytical error for urinary Pyrene metabolite (0.07 ug/L).

Table 2B.

Estimated weighted aGM (95%CI) of uPAHs^(a) at each NHANES cycle. Adjusted for covariates^(b), and stratified by race/ethnicity. Non-Hispanic White (NHW) is the reference group, and compared to Mexican American (MA), Non-Hispanic Black (NHB), and Other/Multi-Racial (Other/Multi.) group, respectively. See Figure 2 for graphical representation of the overall trend data and Figure S1 for graphical representation of percentile data.

	NHW			MA				NHB				Other/Multi.
	aGM	Lower 95%CI	Upper 95%CI	aGM	Lower 95%CI	Upper 95%CI	p	aGM	Lower 95%CI	Upper 95%CI	p	aGM	Lower 95%CI	Upper 95%CI	p
uNAP, Overall
2001-02	3.81	3.65	3.97	4.96	4.59	5.32	<0.01	5.78	5.37	6.18	<0.01	4.98	4.45	5.51	<0.01
2003-04	4.85	4.55	5.14	5.62	5.29	5.96		7.35	6.92	7.78		4.49	4.04	4.94
2005-06	5.32	4.98	5.66	6.54	6.06	7.03		8.13	7.65	8.60		6.49	5.72	7.25
2007-08	6.03	5.74	6.31	7.15	6.77	7.53		7.08	6.51	7.65		6.20	5.32	7.08
2009-10	5.46	5.23	5.68	7.23	6.64	7.83		7.73	6.88	8.58		5.78	5.33	6.24
2011-12	4.98	4.75	5.22	7.90	7.41	8.40		9.19	8.53	9.84		6.58	5.59	7.57
2013-14	5.41	5.10	5.72	8.05	7.40	8.70		8.70	8.05	9.34		5.66	5.27	6.05
uNAP, 25th percentile							<0.01				<0.01				0.01
2001-02	2.19	2.01	2.39	3.16	2.92	3.41		3.40	3.02	3.83		3.20	2.54	4.04
2003-04	2.68	2.28	3.14	3.55	3.34	3.78		4.55	4.22	4.90		2.55	1.88	3.45
2005-06	3.18	2.77	3.65	4.09	3.65	4.58		5.29	5.02	5.58		4.43	3.41	5.77
2007-08	3.37	3.10	3.66	4.56	4.10	5.08		4.31	3.89	4.78		3.22	2.70	3.84
2009-10	2.88	2.71	3.07	4.34	3.96	4.77		4.91	4.48	5.38		3.43	2.62	4.49
2011-12	2.71	2.46	2.99	4.56	4.02	5.17		6.10	5.07	7.34		3.23	2.67	3.92
2013-14	2.69	2.35	3.08	4.07	3.53	4.69		5.94	5.38	6.56		2.85	2.61	3.12
uNAP, 50th percentile							<0.01				<0.01				<0.01
2001-02	3.58	3.32	3.87	4.68	4.21	5.20		5.64	5.10	6.24		4.63	4.16	5.16
2003-04	4.58	4.23	4.97	5.42	4.84	6.07		7.06	6.54	7.62		4.47	3.80	5.25
2005-06	5.05	4.77	5.35	6.13	5.58	6.73		7.74	7.34	8.16		6.64	5.73	7.70
2007-08	5.72	5.34	6.13	7.08	6.55	7.66		6.34	5.91	6.81		5.68	4.68	6.89
2009-10	4.95	4.58	5.35	6.81	6.30	7.37		7.36	6.47	8.37		5.07	4.39	5.85
2011-12	4.61	4.26	5.00	7.02	5.97	8.26		8.88	8.19	9.62		5.86	4.56	7.52
2013-14	4.63	4.20	5.10	7.08	6.36	7.87		8.12	7.78	8.47		5.01	4.59	5.48
uNAP, 75th percentile							<0.01				<0.01				<0.01
2001-02	5.07	4.97	5.18	6.76	6.24	7.32		7.42	6.75	8.16		6.66	5.82	7.61
2003-04	6.60	6.32	6.90	7.57	6.92	8.28		9.20	8.77	9.66		5.91	5.31	6.58
2005-06	6.98	6.55	7.44	8.53	8.01	9.08		10.70	9.91	11.55		8.27	7.43	9.20
2007-08	7.99	7.65	8.34	9.71	9.39	10.04		9.18	8.09	10.41		8.22	7.23	9.36
2009-10	7.49	7.17	7.82	9.47	8.68	10.33		9.68	8.66	10.82		7.73	6.97	8.58
2011-12	6.92	6.58	7.27	10.19	9.64	10.78		11.74	11.10	12.43		9.25	8.04	10.65
2013-14	7.49	7.13	7.86	11.33	10.70	11.99		11.08	10.10	12.15		7.34	6.81	7.90
uNAP, 95th percentile							<0.01				<0.01				<0.01
2001-02	7.40	6.90	7.93	9.47	8.57	10.46		11.01	9.49	12.79		8.73	8.13	9.37
2003-04	9.32	8.81	9.86	10.32	9.68	11.01		15.12	12.68	18.02		8.56	7.12	10.29
2005-06	10.70	9.69	11.80	12.20	11.31	13.15		14.74	13.51	16.08		11.96	10.09	14.18
2007-08	12.11	11.66	12.59	12.89	11.17	14.88		14.26	12.61	16.12		12.74	10.70	15.16
2009-10	11.24	10.71	11.80	14.69	12.77	16.88		14.90	13.17	16.85		11.85	10.43	13.46
2011-12	9.89	9.27	10.55	16.42	14.65	18.41		16.57	14.97	18.34		14.13	12.43	16.06
2013-14	11.98	10.91	13.15	16.08	13.42	19.27		16.18	14.76	17.75		12.40	11.37	13.53
uFLU, Overall							0.01				<0.01				0.10
2001-02	0.36	0.34	0.37	0.37	0.33	0.41		0.51	0.47	0.55		0.35	0.30	0.41
2003-04	0.29	0.27	0.31	0.29	0.27	0.31		0.46	0.43	0.48		0.25	0.23	0.27
2005-06	0.32	0.31	0.34	0.28	0.25	0.31		0.43	0.39	0.46		0.29	0.26	0.33
2007-08	0.31	0.29	0.33	0.32	0.30	0.34		0.38	0.35	0.41		0.29	0.25	0.33
2009-10	0.26	0.25	0.27	0.28	0.26	0.30		0.39	0.35	0.43		0.26	0.23	0.28
2011-12	0.24	0.23	0.26	0.29	0.26	0.31		0.40	0.37	0.43		0.29	0.24	0.33
2013-14	0.20	0.19	0.22	0.23	0.21	0.25		0.29	0.26	0.31		0.19	0.17	0.20
uFLU, 25th percentile							<0.01				<0.01				0.68
2001-02	0.20	0.18	0.22	0.22	0.20	0.24		0.31	0.28	0.36		0.21	0.17	0.25
2003-04	0.15	0.12	0.18	0.19	0.17	0.21		0.27	0.24	0.30		0.14	0.09	0.22
2005-06	0.19	0.16	0.22	0.18	0.15	0.20		0.27	0.25	0.28		0.18	0.14	0.23
2007-08	0.17	0.16	0.19	0.20	0.17	0.23		0.25	0.21	0.29		0.15	0.11	0.19
2009-10	0.14	0.12	0.15	0.16	0.15	0.17		0.24	0.21	0.28		0.15	0.13	0.19
2011-12	0.13	0.12	0.14	0.15	0.13	0.18		0.25	0.22	0.28		0.14	0.10	0.18
2013-14	0.10	0.09	0.12	0.11	0.10	0.13		0.20	0.18	0.22		0.10	0.08	0.11
uFLU, 50th percentile							<0.01				<0.01				<0.01
2001-02	0.34	0.32	0.36	0.35	0.31	0.40		0.48	0.44	0.53		0.34	0.27	0.42
2003-04	0.28	0.26	0.31	0.27	0.26	0.29		0.43	0.40	0.45		0.24	0.22	0.27
2005-06	0.31	0.29	0.32	0.25	0.23	0.28		0.39	0.36	0.43		0.30	0.25	0.36
2007-08	0.30	0.27	0.33	0.32	0.29	0.34		0.35	0.32	0.39		0.26	0.22	0.32
2009-10	0.24	0.22	0.25	0.26	0.24	0.28		0.36	0.32	0.40		0.23	0.20	0.26
2011-12	0.22	0.21	0.23	0.27	0.24	0.31		0.38	0.35	0.41		0.24	0.20	0.29
2013-14	0.17	0.16	0.19	0.20	0.18	0.23		0.27	0.25	0.30		0.16	0.14	0.17
uFLU, 75th percentile							<0.01				<0.01				<0.01
2001-02	0.47	0.45	0.49	0.50	0.46	0.55		0.69	0.66	0.72		0.48	0.38	0.61
2003-04	0.40	0.37	0.43	0.38	0.35	0.40		0.59	0.56	0.63		0.32	0.30	0.35
2005-06	0.42	0.40	0.44	0.36	0.33	0.38		0.57	0.53	0.61		0.38	0.33	0.44
2007-08	0.42	0.39	0.45	0.43	0.40	0.45		0.48	0.44	0.53		0.39	0.34	0.45
2009-10	0.36	0.34	0.38	0.37	0.34	0.40		0.51	0.44	0.60		0.34	0.30	0.39
2011-12	0.34	0.31	0.38	0.37	0.35	0.40		0.52	0.50	0.54		0.39	0.34	0.44
2013-14	0.28	0.26	0.30	0.31	0.28	0.34		0.35	0.32	0.37		0.25	0.23	0.27
uFLU, 95th percentile							<0.01				<0.01				<0.01
2001-02	0.71	0.66	0.76	0.72	0.66	0.79		0.96	0.86	1.06		0.62	0.56	0.69
2003-04	0.54	0.50	0.60	0.51	0.45	0.57		0.89	0.81	0.99		0.51	0.45	0.58
2005-06	0.62	0.58	0.66	0.55	0.46	0.66		0.79	0.64	0.98		0.56	0.47	0.67
2007-08	0.64	0.60	0.68	0.58	0.52	0.65		0.78	0.71	0.85		0.62	0.56	0.70
2009-10	0.56	0.52	0.61	0.54	0.50	0.58		0.79	0.70	0.88		0.54	0.48	0.60
2011-12	0.51	0.48	0.56	0.59	0.48	0.72		0.78	0.67	0.91		0.64	0.55	0.74
2013-14	0.47	0.42	0.53	0.48	0.42	0.55		0.55	0.51	0.59		0.43	0.39	0.48
uPHEN, Overall							0.17				<0.01				0.22
2001-02	0.33	0.32	0.34	0.28	0.25	0.31		0.36	0.33	0.4		0.31	0.26	0.36
2003-04	0.31	0.29	0.33	0.28	0.26	0.30		0.41	0.38	0.44		0.27	0.24	0.29
2005-06	0.32	0.31	0.34	0.26	0.23	0.29		0.36	0.33	0.39		0.28	0.25	0.32
2007-08	0.30	0.29	0.32	0.27	0.25	0.29		0.33	0.30	0.36		0.29	0.25	0.32
2009-10	0.29	0.28	0.30	0.25	0.23	0.26		0.33	0.29	0.36		0.25	0.23	0.28
2011-12	0.25	0.24	0.26	0.24	0.21	0.26		0.33	0.31	0.36		0.27	0.23	0.30
2013-14	0.21	0.20	0.23	0.20	0.18	0.22		0.27	0.25	0.29		0.20	0.19	0.21
uPHEN, 25th percentile							<0.01				<0.01				0.60
2001-02	0.19	0.17	0.20	0.17	0.16	0.19		0.22	0.19	0.26		0.18	0.15	0.22
2003-04	0.18	0.14	0.21	0.18	0.16	0.19		0.25	0.24	0.27		0.16	0.12	0.21
2005-06	0.18	0.16	0.21	0.17	0.15	0.19		0.22	0.21	0.24		0.20	0.16	0.25
2007-08	0.17	0.16	0.19	0.17	0.15	0.19		0.21	0.18	0.25		0.15	0.11	0.19
2009-10	0.16	0.14	0.17	0.15	0.14	0.16		0.21	0.19	0.23		0.15	0.12	0.20
2011-12	0.13	0.12	0.15	0.13	0.12	0.14		0.21	0.19	0.24		0.13	0.10	0.17
2013-14	0.11	0.10	0.12	0.10	0.09	0.11		0.18	0.16	0.20		0.10	0.09	0.12
uPHEN, 50th percentile							<0.01				<0.01				0.01
2001-02	0.32	0.29	0.34	0.26	0.23	0.29		0.34	0.31	0.38		0.30	0.25	0.36
2003-04	0.31	0.28	0.34	0.26	0.24	0.28		0.38	0.36	0.40		0.26	0.24	0.29
2005-06	0.31	0.29	0.33	0.24	0.21	0.27		0.34	0.30	0.39		0.28	0.22	0.34
2007-08	0.29	0.27	0.33	0.27	0.25	0.29		0.30	0.27	0.34		0.26	0.22	0.31
2009-10	0.26	0.25	0.28	0.23	0.21	0.25		0.31	0.27	0.35		0.23	0.21	0.26
2011-12	0.23	0.22	0.24	0.22	0.19	0.25		0.31	0.29	0.34		0.24	0.20	0.29
2013-14	0.19	0.17	0.21	0.18	0.16	0.21		0.26	0.24	0.28		0.17	0.15	0.19
uPHEN, 75th percentile							<0.01				<0.01				<0.01
2001-02	0.43	0.41	0.45	0.38	0.34	0.42		0.47	0.42	0.53		0.42	0.34	0.53
2003-04	0.42	0.40	0.45	0.36	0.34	0.39		0.53	0.50	0.56		0.35	0.32	0.39
2005-06	0.42	0.40	0.43	0.34	0.31	0.38		0.47	0.44	0.51		0.36	0.33	0.40
2007-08	0.41	0.38	0.43	0.36	0.34	0.38		0.43	0.39	0.47		0.38	0.32	0.45
2009-10	0.39	0.38	0.41	0.32	0.30	0.35		0.41	0.36	0.47		0.33	0.30	0.37
2011-12	0.35	0.32	0.39	0.31	0.28	0.34		0.42	0.40	0.44		0.37	0.33	0.41
2013-14	0.30	0.27	0.33	0.27	0.25	0.30		0.33	0.30	0.36		0.26	0.24	0.29
uPHEN, 95th percentile							<0.01				<0.01				<0.01
2001-02	0.62	0.57	0.67	0.56	0.47	0.66		0.68	0.61	0.76		0.53	0.51	0.55
2003-04	0.58	0.55	0.61	0.50	0.42	0.60		0.78	0.70	0.87		0.55	0.46	0.65
2005-06	0.60	0.57	0.64	0.50	0.42	0.60		0.66	0.55	0.79		0.52	0.44	0.62
2007-08	0.61	0.59	0.63	0.50	0.47	0.54		0.69	0.62	0.76		0.59	0.52	0.66
2009-10	0.59	0.53	0.65	0.48	0.44	0.53		0.61	0.51	0.73		0.52	0.45	0.61
2011-12	0.50	0.44	0.55	0.48	0.38	0.61		0.64	0.57	0.73		0.58	0.51	0.67
2013-14	0.47	0.42	0.52	0.43	0.37	0.49		0.47	0.43	0.52		0.45	0.41	0.50
uPYR, Overall							<0.01				<0.01				0.11
2001-02	0.04	0.04	0.04	0.05	0.05	0.06		0.06	0.05	0.06		0.06	0.05	0.07
2003-04	0.07	0.07	0.08	0.08	0.08	0.09		0.11	0.11	0.12		0.08	0.07	0.09
2005-06	0.08	0.08	0.09	0.09	0.08	0.10		0.10	0.10	0.11		0.09	0.08	0.10
2007-08	0.11	0.10	0.11	0.12	0.11	0.13		0.12	0.11	0.13		0.12	0.10	0.13
2009-10	0.10	0.10	0.11	0.14	0.13	0.15		0.16	0.14	0.17		0.13	0.12	0.14
2011-12	0.10	0.09	0.10	0.13	0.12	0.14		0.15	0.14	0.15		0.12	0.10	0.13
2013-14	0.12	0.12	0.13	0.14	0.13	0.15		0.15	0.14	0.16		0.13	0.12	0.14
uPYR, 25th percentile (d)							<0.01				<0.01				<0.01
2001-02	0.02	0.02	0.03	0.03	0.03	0.03		0.04	0.03	0.04		0.03	0.03	0.04
2003-04	0.04	0.03	0.05	0.06	0.05	0.06		0.07	0.06	0.07		0.05	0.04	0.08
2005-06	0.05	0.04	0.06	0.06	0.05	0.07		0.06	0.06	0.07		0.06	0.05	0.07
2007-08	0.06	0.05	0.06	0.08	0.07	0.09		0.08	0.07	0.09		0.06	0.05	0.09
2009-10	0.06	0.05	0.06	0.09	0.08	0.10		0.10	0.09	0.11		0.08	0.07	0.10
2011-12	0.05	0.05	0.06	0.07	0.06	0.09		0.09	0.08	0.10		0.06	0.05	0.08
2013-14	0.07	0.06	0.07	0.08	0.06	0.09		0.11	0.10	0.12		0.07	0.06	0.07
uPYR, 50th percentile (d)							<0.01				<0.01				<0.01
2001-02	0.04	0.04	0.04	0.05	0.04	0.06		0.05	0.05	0.06		0.05	0.04	0.06
2003-04	0.07	0.06	0.08	0.08	0.08	0.09		0.10	0.09	0.11		0.07	0.07	0.08
2005-06	0.08	0.07	0.08	0.08	0.08	0.09		0.10	0.09	0.10		0.09	0.07	0.10
2007-08	0.10	0.09	0.11	0.12	0.10	0.13		0.11	0.10	0.13		0.10	0.09	0.12
2009-10	0.09	0.09	0.10	0.14	0.12	0.15		0.14	0.13	0.15		0.12	0.10	0.13
2011-12	0.09	0.08	0.09	0.12	0.11	0.14		0.14	0.13	0.15		0.10	0.09	0.12
2013-14	0.11	0.10	0.12	0.13	0.11	0.15		0.14	0.13	0.15		0.11	0.10	0.12
uPYR, 75th percentile							<0.01				<0.01				<0.01
2001-02	0.06	0.05	0.06	0.07	0.06	0.07		0.07	0.07	0.08		0.08	0.06	0.10
2003-04	0.09	0.09	0.10	0.11	0.10	0.12		0.14	0.14	0.15		0.10	0.09	0.11
2005-06	0.11	0.11	0.11	0.12	0.10	0.13		0.13	0.12	0.14		0.11	0.09	0.13
2007-08	0.14	0.13	0.15	0.16	0.15	0.17		0.15	0.14	0.16		0.14	0.12	0.18
2009-10	0.14	0.13	0.14	0.18	0.17	0.19		0.20	0.17	0.24		0.17	0.15	0.19
2011-12	0.13	0.12	0.14	0.17	0.16	0.19		0.19	0.18	0.20		0.16	0.14	0.18
2013-14	0.16	0.15	0.18	0.19	0.17	0.21		0.19	0.17	0.21		0.17	0.15	0.18
uPYR, 95th percentile							<0.01				<0.01				<0.01
2001-02	0.08	0.08	0.08	0.09	0.08	0.11		0.10	0.09	0.11		0.11	0.10	0.12
2003-04	0.14	0.14	0.15	0.15	0.14	0.16		0.23	0.21	0.25		0.17	0.16	0.19
2005-06	0.16	0.15	0.16	0.17	0.15	0.18		0.20	0.17	0.24		0.16	0.13	0.19
2007-08	0.21	0.19	0.22	0.23	0.22	0.24		0.24	0.21	0.28		0.24	0.20	0.31
2009-10	0.22	0.20	0.24	0.28	0.25	0.31		0.31	0.26	0.38		0.27	0.24	0.30
2011-12	0.21	0.20	0.21	0.27	0.24	0.30		0.29	0.26	0.32		0.26	0.21	0.33
2013-14	0.29	0.26	0.32	0.29	0.25	0.34		0.30	0.28	0.33		0.28	0.26	0.31

^(a)uNAP; sum of urinary Naphthalene metabolites (ug/L). uFLU: sum of urinary Fluorene metabolites (ug/L). uPHEN: sum of urinary Phenanthrene metabolites (ug/L). UPYR: urinary Pyrene metabolites (ug/L).

^(b)Adjusted for urinary creatinine, age, sex, BMI, dietary sources of PAHs, PIR, and seasonality. Interaction term is NHANES cycle##race/ethnicity.

^(c)p-value for the overall trend in weighted aGM between groups across NHANES cycles was assessed by the adjusted Wald test, α = 0.05.

^(d)The delta in trend values between 2001-02 and 2013-14 are within the maximal analytical error for urinary Pyrene metabolite (0.07 ug/L).

Effect Modification by Race/Ethnicity

Overall, effect modification was observed between race/ethnicity and Naphthalene and Pyrene, where Mexican American and Non-Hispanic Black participants had higher concentrations and a greater increase over time, compared to the reference group, Non-Hispanic Whites (NHW; p for trend: < 0.01; Figure 2). The trend in Naphthalene exposure was also higher in the Other/Multi-Racial group compared to NHW, except in 2003-04 (p < 0.01). Effect modification was also observed for Fluorene, where Non-Hispanic Black participants had a higher concentration compared to NHW (p < 0.01) or any other race/ethnic group. Mexican American participants had higher Fluorene exposure compared to NHW, except in 2005-06 (p = 0.01). Effect modification was observed for Phenanthrene, but only in Non-Hispanic Black participants (p < 0.01), who had higher exposure and greater increase over time compared to NHW.

When grouped by 25^th, 50^th, 75^th and 95^th percentiles, effect modification was observed between race/ethnicity and Naphthalene, where Mexican Americans, Non-Hispanic Black, and Other/Multi-Racial participants had higher exposure and a greater increase over time, compared to NHW in all exposure percentiles (p < 0.01; Table 2B). The 25^th, 50th, and 75th percentile of Naphthalene in Mexican American and Non-Hispanic Black participants was comparable to the 50^th, 75^th, and 95th percentile in NHW, respectively. This indicates that Mexican Americans and Non-Hispanic Blacks had far higher Naphthalene exposure, compared to NHW, over this time period. (See Figure S1). Effect modification was observed by race/ethnicity in Fluorene and Phenanthrene at the 25^th, 50^th, 75^th and 95th percentiles in Mexican American, Non-Hispanic Black, and Other/Multi-Racial participants, when compared to NHW (p < 0.01), except for the 25^th percentile in Other/Multi-Racial participants (p = 0.68 and p = 0.60) for Fluorene and Phenanthrene, respectively. Effect modification was also observed by race/ethnicity in Pyrene at 25^th, 50^th, 75^th and 95th percentiles in Mexican American, Non-Hispanic Black, and Other/Multi-Racial participants, compared to NHW at all percentiles (p < 0.01). However, the change in Pyrene concentrations at the 25^th and 50^th percentiles were very small and within the analytical measurement error for this compound.

Effect Modification by Age

Overall, effect modification was observed between age and Naphthalene where adults, age 18+ years, had higher concentrations and a greater increase over time from 2003-04 through 2005-06, compared to children age 6-17 years. However, this trend disappeared after 2007-08, and children experienced the greatest increase in Naphthalene exposure over time, compared to adults (p for trend: <0.01; Table 2A). Effect modification was observed for Pyrene, where children had higher concentrations and experienced a greater increase in Pyrene exposure over time, compared to adults (p for trend: <0.01), although the absolute trend difference was small and within the analytical measurement error for this compound. No effect modification by age was observed for Fluorene or Phenanthrene.

When grouped by the 25^th, 50^th, 75^th and 95^th percentiles, effect modification was observed between age and Naphthalene, where adults generally had higher exposure, compared to children (p < 0.01; Figure 3). However, at the 95^th percentile, the trend in Naphthalene change and children had the greatest increase in exposure. Although the absolute difference in Pyrene was small, from 2001-02 through 2013-14, the 95^th percentile exposure trend tripled in both children and adults; from 0.11 ug/L, [95%CI: 0.10, 0.12] to 0.33 ug/L, [0.31, 0.36; p < 0.01], and from 0.08 ug/L, [0.07, 0.09] to 0.25 ug/L, [0.23, 0.27; p < 0.01], in children and adults, respectively.

Figure 3.

Trends in uPAH metabolites for children 6-17 years and adults 18+ years, in U.S. non-smokers, 2001-2014. Weighted aGM and 95% confidence interval (95%CI) for each NHANES cycle estimated from linear regression models adjusted for urinary creatinine, sex, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality; interaction term is NHANES cycle##age. (A) uNAP: sum of urinary Naphthalene metabolites (1- & 2-naphthol), n = 11,028. (B) uFLU: sum of urinary Fluorene metabolites (2- & 3-fluorene), n = 10,989. (C) uPHEN: sum of urinary Phenanthrene metabolites (1-, 2- & 3-phenanthrene), n = 11,012. (D) uPYR: urinary Pyrene metabolites, n = 10,955. See Table 2A for more information.

^(‡) The delta in trend values between 2001-02 and 2013-14 for the 25^th and 50^th percentiles are within the maximal analytical error for urinary Pyrene metabolite (0.07 ug/L).

Effect Modification by Sex

Overall, effect modification was observed between sex and Fluorene where males, age 6+ years, had higher concentrations compared to females (p < 0.01, Table 2A). Males also had higher concentrations of Pyrene, compared to females (p for trend: <0.01), although the absolute difference in the overall trend was small and within the analytical measurement error of uPYR. Overall, no effect modification by sex was observed for Naphthalene or Phenanthrene.

When grouped by 25^th, 50^th, 75^th and 95^th percentiles, effect modification was observed in Fluorene and Phenanthrene exposure, where males had higher exposure, compared to females (p for trend: < 0.01; Figure 4). Effect modification was also observed by sex and Naphthalene, where males had higher exposure in the 25^th, 50^th and 75^th percentiles (p for trend: < 0.01), and in the 95^th percentile until 2007-08, but this trend reversed and females had higher Naphthalene exposure between 2009-10 to 2013-14 (p for trend: < 0.01). Also, in 2011-12, the 95^th percentile of Naphthalene exposure was significantly higher in females (12.9 ug/L [12.1, 13.8]), compared to males (11.3 ug/L, [10.7, 12.0; p < 0.05]). For Pyrene, effect modification was observed in the 75^th percentile, where males had higher exposure, and greater increase in exposure over time, compared to females (p for trend < 0.01). In the 95^th percentile, males had higher Pyrene exposure until 2005-06, then females had higher Pyrene exposure, and greater increase in exposure through 2013-14, compared to males (p for trend < 0.01).

Figure 4.

Trends in uPAH metabolites for males and females, age 6+ years, in U.S. non-smokers, 2001-2014. Weighted aGM and 95% confidence interval (95%CI) for each NHANES cycle estimated from linear regression models adjusted for urinary creatinine, age, race/ethnicity, BMI, dietary sources of PAHs, PIR, and seasonality; interaction term is NHANES cycle##sex. (A) uNAP: sum of urinary Naphthalene metabolites (1- & 2-naphthol), n = 11,028. (B) uFLU: sum of urinary Fluorene metabolites (2- & 3-fluorene), n = 10,989. (C) uPHEN: sum of urinary Phenanthrene metabolites (1-, 2- & 3-phenanthrene), n = 11,012. (D) uPYR: urinary Pyrene metabolites, n = 10,955. See Table 2A for more information.

^(‡) The delta in trend values between 2001-02 and 2013-14 for the 25^th and 50^th percentiles are within the maximal analytical error for urinary Pyrene metabolite (0.07 ug/L).

Overall, effect modification was observed between the sexes at reproductive age (age 18-49 years) and Naphthalene, Fluorene, Phenanthrene, and Pyrene (p < 0.01, respectively; Table 2A). Compared to men, women had lower Naphthalene exposure from 2001-02 to 2003-04, and in 2007-08, but had higher exposure in 2005-06, after 2009-10 (p for trend: < 0.01). Women of reproductive age had lower Fluorene, Phenanthrene and Pyrene exposure trends, compared to men in the same age range, across NHANES cycles (p for trend: 0.01).

When grouped by the 25^th, 50^th, 75^th and 95^th percentiles, effect modification between the sexes at reproductive age and Naphthalene, Fluorene, Phenanthrene, and Pyrene was observed in all percentiles (p < 0.01; Figure 5). Compared to men age 18-49 years, women in the same age range generally had lower Naphthalene exposure in the 50^th and the 75^th percentiles, except in 2005-06 and 2013-14 (p for trend: < 0.01). Women had higher Naphthalene exposure in the 25^th and 95^th percentiles in 2005-06 and after 2007-08 (p for trend: < 0.01). Women of reproductive age also had a lower Fluorene exposure trend, compared to men, except in 2009-10 and 2013-14 in the 75^th and 95^th percentiles (p for trend: < 0.01). For Phenanthrene, women of reproductive age had a higher exposure trend in the 75^th percentile in 2009-10 and 2013-14 (p for trend: 0.01), and in the 95^th percentile after 2007-08 (p for trend < 0.01). For Pyrene, women of reproductive age generally had lower exposure in the 25^th and 50^th percentiles (p for trend: < 0.01), but higher exposure in the 75^th percentile in 2009-10 and 2013-14 (p for trend: < 0.01), and in the 95^th percentile after 2005-06 (p for trend: < 0.01). These results suggest a trend of increasing PAH exposure at the higher exposure levels for non-smoking U.S. women of reproductive age.

Sensitivity analyses were performed among the subset of participants who had work-related and housing characteristics data (Tables S4 and S5 in the Supplemental Information, respectively.) The overall results from the sensitivity analyses were consistent with the main analyses.

4. DISCUSSION

The widespread dispersion of PAHs in the environment and their toxic effects have made these compounds the focus for public health surveillance and regulatory action. Our trend analysis of the U.S. non-smoking population found that overall, when grouped by percentiles, and across age, sex and race/ethnicity groups, Naphthalene and Pyrene exposure increased between 2001-2014, while Fluorene and Phenanthrene exposure decreased. We also found significant differences in PAH exposure based on race/ethnicity. Our study showed that Non-Hispanic Black participants had higher Naphthalene, Fluorene, Phenanthrene and Pyrene exposure, and Mexican American participants had higher Naphthalene, Fluorene, and Pyrene exposure, as well as greater increases in exposure over time, compared to Non-Hispanic Whites. Our results also showed a changing trend in Naphthalene exposure where children experienced a greater increase in exposure in more recent years, compared to adults.

Although we hypothesized that females would have lower PAH exposure, our findings revealed that the trend in Naphthalene was highest in females 6+ years of age at the 95^th percentile after 2005-06, compared to males. In addition, women 18-49 years generally had higher exposure to Naphthalene and Pyrene at the 75^th and 95th percentile, compared to men. This last finding is of particular interest because research shows PAHs can affect fertility (37) and can cross the placenta and can have adverse health effects in infants and children (38).

Our results are consistent with findings from previous studies examining PAH exposure in the U.S. Hendryx and Luo (2017) used NHANES data from 2003-2012 to evaluate the trend in uPAHs in U.S. children 6-19 years of age (39). They found that the 2-naphthol, 2-hydroxyphenanthrene, and 1-hydroxypyrene increased over the time period, while 1-naphthol and 3-hydroxyphenanthrene decreased (39). We also saw increases in Naphthalene and Pyrene in our study, but our analysis combined 1-, 2- and 3-hydroxyphenanthrene into a single biomarker since these urinary metabolites are derived from the same parent compound, uPHEN, which we observed a decrease from 2001-2014. We also observed that Mexican Americans and Non-Hispanic Blacks, and Other/Multi-Racial participants had higher overall Naphthalene and Pyrene exposure, compared to Non-Hispanic Whites. Mexican Americans and Non-Hispanic Blacks also had higher Fluorene exposure, and Non-Hispanic Blacks had higher Phenanthrene exposure, compared to Non-Hispanic Whites. Given the health effects of PAH exposures, it is important that future studies explore why non-smokers in these race/ethnicity groups have higher uPAHs.

In relation to previous studies that evaluated PAH exposure in the U.S. with urinary biomarkers, our findings show that Naphthalene and Pyrene exposure is increasing, although the absolute differences are small. Hill, et al., (1995), utilized NHANES III (1988-1994, non-random sample data) data to examine pesticide residues in urine of adults 20-59 years of age, and reported creatinine-corrected 1-naphthol, and 2-naphthol mean concentrations of 15, and 5.4 ug/g, respectively (40). However, the authors did not state if their analyses were adjusted for tobacco smoke exposure. Buckley, et al. (1997), reported that 18 non-smoking adults living near Brownsville, TX during the spring and summer of 1993, had a 1-naphthol, 2-naphthol, and 1-hydroxypyrene creatinine-corrected median concentration of 2.8, 2.6 ug/L (both spring and summer), and 0.01 ug/L(spring) and 0.05 ug/L (summer), respectively. Compared to our study, these values equate to the uNAP concentration (aGM) we observed prior to 2005-06, and the uPYR concentration we observed prior to 2007-08. In the 1999-2000 NHANES cycle, the CDC reported creatinine-corrected geometric mean (95%CI) of uNAP was 1.96 ug/g (1.50, 2.45), uFLU: 0.57 ug/g (0.42, 0.77), uPHEN: (0.35 ug/g (0.29, 0.41), and uPYR: 0.07 ug/g (0.06, 0.09) (41). The analyses were not adjusted for tobacco smoke exposure, and the age range for the 1999-2000 NHANES measure of uNAP was 6-59 years. Data for the PAH metabolites of interest for our study were not publicly available for the 1999-2000 NHANES cycle. These studies and reports suggest that human exposure to Naphthalene may have decreased from the time of the Hill and Buckley studies, but has increased since 1999-2000. Pyrene exposure has also increased since Buckley, although the absolute difference is 0.04 ug/L, which is within the range of the maximal analytical measurement error of 0.07 ug/L Fluorene and Phenanthrene exposure has decreased since 1999-2000 and the difference is above the analytical measurement error, but again, the absolute difference is small.

Our findings are similar to the trends observed in previously mentioned studies that evaluated PAH in ambient air in the U.S., suggesting that ambient air is an important source of PAH exposure for non-smokers (20,22,24). By examining the difference in PAH ambient concentrations during the week compared to the weekend from 1990-2014, Liu, et al. found that a major contributor to temporal changes in Naphthalene and Pyrene in urban ambient air was diesel engine exhaust (22). This finding may be influenced by the different phase-in schedules to reduce vehicle emissions under the U.S. Clean Air Act Amendments of 1990. Light-duty engines that tend to use gasoline were in scope of the emission standard beginning in 1994, whereas the phase-in schedule for larger engines that tend to use diesel began in 2004 and will continue based on engine size through 2025 (42). In addition to PAHs, vehicle emissions, especially from diesel fuel, can produce ultrafine particulate matter (PM_2.5), which suspends in ambient air (43). More stringent U.S. federal PM_2.5 air quality standards since 1997 have helped reduce ambient PM_2.5 concentrations by 43% from 2000 to 2019 (44), and subsequently may have contributed to an overall decrease in PAHs in ambient air. The recent U.S. regulatory action to reduce mercury emissions from coal-fired power plants (i.e., the Mercury Air Toxics Standards or MATS, 2012) may also contribute to the observed PAHs decreases in ambient air.

Indoor environments are also likely to be an important source of PAH exposure for non-smokers. Naumova, et al. (2002) and Johnson, et al. (2010) found that PAHs were actually higher in indoor air in non-smoking homes than in outdoor air (45,46). Shin, et al., (2013) modeled indoor and outdoor PAH emissions with uPAH biomarker data from the 2001-02 NHANES survey and found the estimated dose of Naphthalene, Fluorene, Phenanthrene, and Pyrene inferred from urinary biomarkers closely matched the z-scores of modeled indoor air inhalation (25). PAHs in indoor are can come from many sources. For instance, Naphthalene is used to make polyvinyl chloride and high levels have been detected in vinyl- and foam-based home products (47). Kang, et al., (2012) found that some vinyl home furnishings had higher Naphthalene content than mothballs (47). In addition, use of natural gas appliances and heating are major sources of PAHs in non-smoking homes (48).

House dust can be another source of PAH exposure in the indoor environment. Whitehead, et al., analyzed PAHs in the dust collected from California homes and found the median concentration of Phenanthrene and Pyrene in 290 homes, 2001-2007, was 120 ng/g and 160 ng/g, respectively (49). In a follow-up study in 2010, the authors found that median concentration of Phenanthrene in 204 homes had decreased to 100 ng/g, but Pyrene concentration had increased to 190 ng/g (49). A similar trend was seen in a New York birth cohort study that measured PAHs in indoor air, and uPAHs in children 3 years of age from 2001-2009 (n=409), and found the GM concentration of 1-napthol decreased by 44%, but 2-naphthol and Pyrene increased 162% and 46%, respectively (8 Supplementary Material). Our findings are consistent with the results of these indoor air PAH trend studies.

Regulatory actions at the federal level tend to be more focused on reducing environmental toxics in ambient air, while building codes are meant to address indoor environmental factors, although these codes are not uniformly applied across the U.S. However, modern humans in the U.S. spend over 90% of their time indoors (50), and monitoring the indoor air environment is a public health challenge. Unlike ambient air, the indoor air environment is susceptible to several factors including ventilation, age of home, lifestyle choices (smoking, burning candles or incense, etc.), indoor combustion sources (e.g., stoves, furnaces, fireplaces, etc.), outgassing of structural building materials, and use of personal products. PAH exposure from indoor air is especially concerning for women and children, who tend to spend more time indoors compared to men (50).

The strength of this study lies in the high quality of NHANES procedures and laboratory analyses, the large sample size that supports a well powered analysis, the application of survey design variables that make the results generalizable to the U.S. non-smoking population, and the 14-year time period to evaluate PAH exposure trends. The limitations to this cross-sectional study design is that biomarkers cannot identify the source of exposure because they integrate personal exposures from all sources. The short half-life of PAHs mean that a spot urine sample only reflects recent exposures. Our analysis was limited to the PAH metabolite data made publicly available for analysis by the NCHS. In addition, data on work and housing characteristic data was not available for all NHANES cycles of interest, which limited our ability to control for these variables in our trend analysis.

5. Conclusion

This study illustrates that efforts to reduce PAH exposure have not had uniform effects among non-smoking U.S. residents, 2001-2014. Specifically, our findings that Naphthalene and Pyrene exposure increased over the study period indicate control measures in the U.S. have fallen short, especially in reducing these exposures in children, females, people of reproductive age, and racial/ethnic minorities. Further research is needed to fully understand the sources of PAHs to allow for more effective ways of controlling exposure.

Highlights.

• Polycyclic aromatic hydrocarbons are ubiquitous environmental pollutants

• Urinary PAH metabolites detected in 96% of U.S. non-smokers, age 6+ years, 2001-14

• In U.S. non-smokers 2001-14, exposure to Naphthalene and Pyrene increased

• In U.S. non-smokers 2001-14, exposure to Fluorene and Phenanthrene decreased

• In U.S. non-smokers 2001-14, Non-Hispanic Blacks had highest PAH exposures