Debra A. Trinidad

Excretion Profiles and Half-Lives of Ten Urinary Polycyclic Aromatic Hydrocarbon Metabolites after Dietary Exposure

Human exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed by biomonitoring of their urinary monohydroxylated metabolites (OH-PAHs). Limited information exists on the human pharmacokinetics of OH-PAHs. This study aimed to investigate the excretion half-life of 1-hydroxypyrene (1-PYR), the most used biomarker for PAH exposure, and 9 other OH-PAHs following a dietary exposure in 9 nonsmoking volunteers with no occupational exposure to PAHs. Each person avoided food with known high PAH-content during the study period, except for a high PAH-containing lunch (barbecued chicken) on the first day. Individual urine samples (n = 217) were collected from 15 h before to 60 h following the dietary exposure. Levels of all OH-PAHs in all subjects increased rapidly by 9-141-fold after the exposure, followed by a decrease consistent with first-order kinetics, and returned to background levels 24-48 h after the exposure. The average time to reach maximal concentration ranged from 3.1 h (1-naphthol) to 5.5 h (1-PYR). Creatinine-adjusted urine concentrations for each metabolite were analyzed using a nonlinear mixed effects model including a term to estimate background exposure. The background-adjusted half-life estimate was 3.9 h for 1-PYR and ranged 2.5-6.1 h for the other 9 OH-PAHs, which in general, were shorter than those previously reported. The maximum concentrations after barbecued chicken consumption were comparable to the levels found in reported occupational settings with known high PAH exposures. It is essential to consider the relatively short half-life, the timing of samples relative to exposures, and the effect of diet when conducting PAH exposure biomonitoring studies.

Variability of urinary concentrations of polycyclic aromatic hydrocarbon metabolite in general population and comparison of spot, first-morning, and 24-h void sampling.

Urinary mono-hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are commonly used in biomonitoring to assess exposure to polycyclic aromatic hydrocarbons (PAHs). Similar to other biologically non-persistent chemicals, OH-PAHs have relatively short biological half-lives (4.4-35 h). Little information is available on their variability in urinary concentrations over time in non-occupationally exposed subjects. This study was designed to (i) examine the variability of nine urinary OH-PAH metabolite concentrations over time and (ii) calculate sample size requirements for future epidemiological studies on the basis of spot urine, first-morning void, and 24-h void sampling. Individual urine samples (n=427) were collected during 1 week from 8 non-occupationally exposed adults. We recorded the time and volume of each urine excretion, dietary details, and driving activities of the participants. Within subjects, the coefficients of variation (CVs) for the wet-weight concentration of OH-PAHs in all samples ranged from 45% to 297%; creatinine adjustment reduced the CV to 19-288% (P<0.001; paired t-test). The simulated 24-h void concentrations were the least variable measure, with CVs ranging from 13% to 182% for the 9 OH-PAHs. Within-day variability contributed on average 84%, and between-day variability accounted for 16% of the total variance of 1-hydroxypyrene (1-PYR). Intraclass correlation coefficients of 1-PYR levels were 0.55 for spot urine samples, 0.65 [corrected] for first-morning voids, and 0.77 [corrected] for 24-h voids, indicating a high degree of correlation between urine measurements collected from the same subject over time. Sample size calculations were performed to estimate the number of subjects required for detecting differences in the geometric mean at a statistical power of 80% for spot urine, first-morning, and 24-h void sampling. These data will aid in the design of future studies of PAHs and possibly other biologically non-persistent chemicals and in the interpretation of their analytical results.Urinary mono-hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are commonly used in biomonitoring to assess exposure to polycyclic aromatic hydrocarbons (PAHs). Similar to other biologically non-persistent chemicals, OH-PAHs have relatively short biological half-lives (4.4–35 h). Little information is available on their variability in urinary concentrations over time in non-occupationally exposed subjects. This study was designed to (i) examine the variability of nine urinary OH-PAH metabolite concentrations over time and (ii) calculate sample size requirements for future epidemiological studies on the basis of spot urine, first-morning void, and 24-h void sampling. Individual urine samples (n=427) were collected during 1 week from 8 non-occupationally exposed adults. We recorded the time and volume of each urine excretion, dietary details, and driving activities of the participants. Within subjects, the coefficients of variation (CVs) for the wet-weight concentration of OH-PAHs in all samples ranged from 45% to 297%; creatinine adjustment reduced the CV to 19–288% (P<0.001; paired t-test). The simulated 24-h void concentrations were the least variable measure, with CVs ranging from 13% to 182% for the 9 OH-PAHs. Within-day variability contributed on average 84%, and between-day variability accounted for 16% of the total variance of 1-hydroxypyrene (1-PYR). Intraclass correlation coefficients of 1-PYR levels were 0.55 for spot urine samples, 0.60 for first-morning voids, and 0.76 for 24-h voids, indicating a high degree of correlation between urine measurements collected from the same subject over time. Sample size calculations were performed to estimate the number of subjects required for detecting differences in the geometric mean at a statistical power of 80% for spot urine, first-morning, and 24-h void sampling. These data will aid in the design of future studies of PAHs and possibly other biologically non-persistent chemicals and in the interpretation of their analytical results.

Urinary Polycyclic Aromatic Hydrocarbon Metabolites as Biomarkers to Woodsmoke Exposure – Results from a Controlled Exposure Study

Woodsmoke contains harmful components — such as fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) — and impacts more than half of the global population. We investigated urinary hydroxylated PAH metabolites (OH-PAHs) as woodsmoke exposure biomarkers in nine non-smoking volunteers experimentally exposed to a wood fire. Individual urine samples were collected from 24-h before to 48-h after the exposure and personal PM2.5 samples were collected during the 2-h woodsmoke exposure. Concentrations of nine OH-PAHs increased by 1.8–7.2 times within 2.3–19.3 h, and returned to baseline approximately 24 h after the exposure. 2-Naphthol (2-NAP) had the largest post-exposure increase and exhibited a clear excretion pattern in all participants. The level of urinary OH-PAHs, except 1-hydroxypyrene (1-PYR), correlated with those of PM2.5, levoglucosan and PAHs in personal PM2.5 samples. This finding suggests that several urinary OH-PAHs, especially 2-NAP, are potential exposure biomarkers to woodsmoke; by contrast, 1-PYR may not be a suitable biomarker. Compared with levoglucosan and methoxyphenols — two other urinary woodsmoke biomarkers that were measured in the same study and reported previously — OH-PAHs might be better biomarkers based on sensitivity, robustness and stability, particularly under suboptimal sampling and storage conditions, like in epidemiological studies carried out in less developed areas.

Biomonitoring Human Exposure to Household Air Pollution and Association with Self-reported Health Symptoms – A Stove Intervention Study in Peru

BACKGROUND Household air pollution (HAP) from indoor biomass stoves contains harmful pollutants, such as polycyclic aromatic hydrocarbons (PAHs), and is a leading risk factor for global disease burden. We used biomonitoring to assess HAP exposure and association with self-reported symptoms in 334 non-smoking Peruvian women to evaluate the efficacy of a stove intervention program. METHODS We conducted a cross-sectional study within the framework of a community randomized control trial. Using urinary PAH metabolites (OH-PAHs) as the exposure biomarkers, we investigated whether the intervention group (n=155, with new chimney-equipped stoves) were less exposed to HAP compared to the control group (n=179, with mostly open-fire stoves). We also estimated associations between the exposure biomarkers, risk factors, and self-reported health symptoms, such as recent eye conditions, respiratory conditions, and headache. RESULTS We observed reduced headache and ocular symptoms in the intervention group than the control group. Urinary 2-naphthol, a suggested biomarker for inhalation PAH exposure, was significantly lower in the intervention group (GM with 95% CI: 13.4 [12.3, 14.6] μg/g creatinine) compared to control group (16.5 [15.0, 18.0] μg/g creatinine). Stove type and/or 2-naphthol was associated with a number of self-reported symptoms, such as red eye (adjusted OR with 95% CI: 3.80 [1.32, 10.9]) in the past 48h. CONCLUSIONS Even with the improved stoves, the biomarker concentrations in this study far exceeded those of the general populations and were higher than a no-observed-genotoxic-effect-level, indicating high exposure and a potential for increased cancer risk in the population.