Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.

BACKGROUND: We evaluated cancer incidence in a cohort of polychlorinated biphenyl (PCB) exposed workers. METHODS: Incident cancers, identified using state registries, were compared to those in a national population using standardized incidence ratios. Trends in prostate cancer incidence with cumulative PCB exposure were evaluated using standardized rate ratios and Cox regression models. For selected sites, cumulative PCB exposure was compared between aggressive (fatal/distant stage) and localized/regional cancers. RESULTS: We identified 3,371 invasive first primary cancer diagnoses among 21,317 eligible workers through 2007. Overall relative incidence was reduced. Elevations were only observed for respiratory cancers and among women, urinary organ cancers. Among men, prostate cancer incidence was reduced and not associated with cumulative PCB exposure although median exposures were significantly higher for aggressive compared to localized/regional prostate cancers. CONCLUSION: Previously observed associations between cumulative PCB exposure and prostate cancer mortality were not confirmed in this analysis; prostate cancer stage at diagnosis may explain the discrepancy.

Although polychlorinated biphenyls (PCBs) have been banned in many countries for more than three decades, exposures to PCBs continue to be of concern due to their long half-lives and carcinogenic effects. In National Institute for Occupational Safety and Health studies, we are using semiquantitative plant-specific job exposure matrices (JEMs) to estimate historical PCB exposures for workers (n = 24,865) exposed to PCBs from 1938 to 1978 at three capacitor manufacturing plants. A subcohort of these workers (n = 410) employed in two of these plants had serum PCB concentrations measured at up to four times between 1976 and 1989. Our objectives were to evaluate the strength of association between an individual worker's measured serum PCB levels and the same worker's cumulative exposure estimated through 1977 with the (1) JEM and (2) duration of employment, and to calculate the explained variance the JEM provides for serum PCB levels using (3) simple linear regression. Consistent strong and statistically significant associations were observed between the cumulative exposures estimated with the JEM and serum PCB concentrations for all years. The strength of association between duration of employment and serum PCBs was good for highly chlorinated (Aroclor 1254/HPCB) but not less chlorinated (Aroclor 1242/LPCB) PCBs. In the simple regression models, cumulative occupational exposure estimated using the JEMs explained 14-24% of the variance of the Aroclor 1242/LPCB and 22-39% for Aroclor 1254/HPCB serum concentrations. We regard the cumulative exposure estimated with the JEM as a better estimate of PCB body burdens than serum concentrations quantified as Aroclor 1242/LPCB and Aroclor 1254/HPCB.

We developed a semiquantitative job exposure matrix (JEM) for workers exposed to polychlorinated biphenyls (PCBs) at a capacitor manufacturing plant from 1946 to 1977. In a recently updated mortality study, mortality of prostate and stomach cancer increased with increasing levels of cumulative exposure estimated with this JEM (trend p values = 0.003 and 0.04, respectively). Capacitor manufacturing began with winding bales of foil and paper film, which were placed in a metal capacitor box (pre-assembly), and placed in a vacuum chamber for flood-filling (impregnation) with dielectric fluid (PCBs). Capacitors dripping with PCB residues were then transported to sealing stations where ports were soldered shut before degreasing, leak testing, and painting. Using a systematic approach, all 509 unique jobs identified in the work histories were rated by predetermined process- and plant-specific exposure determinants; then categorized based on the jobs' similarities (combination of exposure determinants) into 35 job exposure categories. The job exposure categories were ranked followed by a qualitative PCB exposure rating (baseline, low, medium, and high) for inhalation and dermal intensity. Category differences in other chemical exposures (solvents, etc.) prevented further combining of categories. The mean of all available PCB concentrations (1975 and 1977) for jobs within each intensity rating was regarded as a representative value for that intensity level. Inhalation (in microgram per cubic milligram) and dermal (unitless) exposures were regarded as equally important. Intensity was frequency adjusted for jobs with continuous or intermittent PCB exposures. Era-modifying factors were applied to the earlier time periods (1946-1974) because exposures were considered to have been greater than in later eras (1975-1977). Such interpolations, extrapolations, and modifying factors may introduce non-differential misclassification; however, we do believe our rigorous method minimized misclassification, as shown by the significant exposure-response trends in the epidemiologic analysis.

The objective of this analysis was to evaluate mortality among a cohort of 24,865 capacitor-manufacturing workers exposed to polychlorinated biphenyls (PCBs) at plants in Indiana, Massachusetts, and New York and followed for mortality through 2008. Cumulative PCB exposure was estimated using plant-specific job-exposure matrices. External comparisons to US and state-specific populations used standardized mortality ratios, adjusted for gender, race, age and calendar year. Among long-term workers employed 3 months or longer, within-cohort comparisons used standardized rate ratios and multivariable Poisson regression modeling. Through 2008, more than one million person-years at risk and 8749 deaths were accrued. Among long-term employees, all-cause and all-cancer mortality were not elevated; of the a priori outcomes assessed only melanoma mortality was elevated. Mortality was elevated for some outcomes of a priori interest among subgroups of long-term workers: all cancer, intestinal cancer and amyotrophic lateral sclerosis (women); melanoma (men); melanoma and brain and nervous system cancer (Indiana plant); and melanoma and multiple myeloma (New York plant). Standardized rates of stomach and uterine cancer and multiple myeloma mortality increased with estimated cumulative PCB exposure. Poisson regression modeling showed significant associations with estimated cumulative PCB exposure for prostate and stomach cancer mortality. For other outcomes of a priori interest - rectal, liver, ovarian, breast, and thyroid cancer, non-Hodgkin lymphoma, Alzheimer disease, and Parkinson disease - neither elevated mortality nor positive associations with PCB exposure were observed. Associations between estimated cumulative PCB exposure and stomach, uterine, and prostate cancer and myeloma mortality confirmed our previous positive findings.

Polychlorinated biphenyls (PCBs) are carcinogenic. Estimating PCB half-life in the body based on levels in sera from exposed workers is complicated by the fact that occupational exposure to PCBs was to commercial PCB products (such as Aroclors 1242 and 1254) comprised of varying mixtures of PCB congeners. Half-lives were estimated using sera donated by 191 capacitor manufacturing plant workers in 1976 during PCB use (1946-1977), and post-exposure (1979, 1983, and 1988). Our aims were to: (1) determine the role of covariates such as gender on the half-life estimates, and (2) compare our results with other published half-life estimates based on exposed workers. All serum PCB levels were adjusted for PCB background levels. A linear spline model with a single knot was used to estimate two separate linear equations for the first two serum draws (Equation A) and the latter two (Equation B). Equation A gave half-life estimates of 1.74 years and 6.01 years for Aroclor 1242 and Aroclor 1254, respectively. Estimates were 21.83 years for Aroclor 1242 and 133.33 years for Aroclor 1254 using Equation B. High initial body burden was associated with rapid PCB elimination in workers at or shortly after the time they were occupationally exposed and slowed down considerably when the dose reached background PCB levels. These concentration-dependent half-life estimates had a transition point of 138.57 and 34.78 ppb for Aroclor 1242 and 1254, respectively. This result will help in understanding the toxicological and epidemiological impact of exposure to PCBs in humans. (2012 Elsevier Ltd.)

PURPOSE: Diisononyl phthalate (DiNP) is primarily used as a plasticizer in polyvinyl chloride (PVC) materials. While information is available on general population exposure to DiNP, occupational exposure data are lacking. We present DiNP metabolite urinary concentrations in PVC processing workers, estimate DiNP daily intake for these workers, and compare worker estimates to other populations. METHODS: We assessed DiNP exposure in participants from two companies that manufactured PVC materials, a PVC film manufacturer (n = 25) and a PVC custom compounder (n = 12). A mid-shift and end-shift urine sample was collected from each participant and analyzed for the DiNP metabolite mono(carboxy-isooctyl) phthalate (MCiOP). Mixed models were used to assess the effect on MCiOP concentrations of a worker being assigned to (1) a task using DiNP and (2) a shift where DiNP was used. A simple pharmacokinetic model was used to estimate DiNP daily intake from the MCiOP concentrations. RESULTS: Creatinine-adjusted MCiOP urinary concentrations ranged from 0.42-80 mcg/g in PVC film and from 1.11-13.4 mcg/g in PVC compounding. PVC film participants who worked on a task using DiNP (n = 7) had the highest MCiOP geometric mean (GM) end-shift concentration (25.2 mcg/g), followed by participants who worked on a shift where DiNP was used (n = 11) (17.7 mcg/g) as compared to participants with no task (2.92 mcg/g) or shift (2.08 mcg/g) exposure to DiNP. The GM end-shift MCiOP concentration in PVC compounding participants (4.80 mcg/g) was comparable to PVC film participants with no task or shift exposure to DiNP. Because no PVC compounding participants were assigned to tasks using DINP on the day sampled, DiNP exposure in this company may be underestimated. The highest DiNP intake estimate was 26 mcg/kg/day. CONCLUSION: Occupational exposure to DiNP associated with PVC film manufacturing tasks were substantially higher (sixfold to tenfold) than adult general population exposures; however, all daily intake estimates were less than 25% of current United States or European acceptable or tolerable daily intake estimates. Further characterization of DiNP occupational exposures in other industries is recommended.

BACKGROUND: Though commercial production of polychlorinated biphenyls was banned in the United States in 1977, exposure continues due to their environmental persistence. Several studies have examined the association between environmental polychlorinated biphenyl exposure and modulations of the secondary sex ratio, with conflicting results. OBJECTIVE: Our objective was to evaluate the association between maternal preconceptional occupational polychlorinated biphenyl exposure and the secondary sex ratio. METHODS: We examined primipara singleton births of 2595 women, who worked in three capacitor plants at least one year during the period polychlorinated biphenyls were used. Cumulative estimated maternal occupational polychlorinated biphenyl exposure at the time of the infant's conception was calculated from plant-specific job-exposure matrices. A logistic regression analysis was used to evaluate the association between maternal polychlorinated biphenyl exposure and male sex at birth (yes/no). RESULTS: Maternal body mass index at age 20, smoking status, and race did not vary between those occupationally exposed and those unexposed before the child's conception. Polychlorinated biphenyl-exposed mothers were, however, more likely to have used oral contraceptives and to have been older at the birth of their first child than non-occupationally exposed women. Among 1506 infants liveborn to polychlorinated biphenyl-exposed primiparous women, 49.8% were male; compared to 49.9% among those not exposed (n = 1089). Multivariate analyses controlling for mother's age and year of birth found no significant association between the odds of a male birth and mother's cumulative estimated polychlorinated biphenyl exposure to time of conception. CONCLUSIONS: Based on these data, we find no evidence of altered sex ratio among children born to primiparous polychlorinated biphenyl-exposed female workers.

OBJECTIVES: There are some common occupational agents and exposure circumstances where evidence of carcinogenicity is substantial but not yet conclusive for humans. The objectives are to identify research gaps and needs for twenty agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. DATA SOURCES: A systematic review was conducted of new data published since the most recent pertinent IARC monograph meeting. DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress and immuno- and hormonal modulation. CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

BACKGROUND: Polychlorinated biphenyls (PCBs) are considered probable human carcinogens by the International Agency for Research on Cancer and one congener, PCB 126, has been rated as a known human carcinogen. A period-specific job exposure matrix (JEM) was developed for former PCB-exposed capacitor manufacturing workers (n=12,605) (1938-1977). METHODS: A detailed exposure assessment for this plant was based on a number of exposure determinants (proximity, degree of contact with PCBs, temperature, ventilation, process control, job mobility). The intensity and frequency of PCB exposures by job for both inhalation and dermal exposures, and additional chemical exposures were reviewed. The JEM was developed in nine steps: (1) all unique jobs (n=1,684) were assessed using (2) defined PCB exposure determinants; (3) the exposure determinants were used to develop exposure profiles; (4) similar exposure profiles were combined into categories having similar PCB exposures; (5) qualitative intensity (high-medium-low-baseline) and frequency (continuous-intermittent) ratings were developed, and (6) used to qualitatively rate inhalation and dermal exposure separately for each category; (7) quantitative intensity ratings based on available air concentrations were developed for inhalation and dermal exposures based on equal importance of both routes of exposure; (8) adjustments were made for overall exposure, and (9) for each category the product of intensity and frequency was calculated, and exposure in the earlier era was weighted. RESULTS: A period-specific JEM modified for two eras of stable PCB exposure conditions. CONCLUSIONS: These exposure estimates, derived from a systematic and rigorous use of the exposure determinant data, lead to cumulative PCB exposure-response relationships in the epidemiological cancer mortality and incidence studies of this cohort.

Phthalates are used as plasticizers in many industrial and consumer products. Urinary biomonitoring has shown widespread human exposure to phthalates, with workers having especially high exposures. Phthalates can be present in workplace air as either aerosols or vapors depending on source materials, vapor pressure, and processing temperatures. We sought to develop a dual-phase air sampling method for 6 phthalates, dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BzBP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP), adaptable to aerosol inlets with known particle collection characteristics. Collection media consisted of a quartz fiber filter and XAD-2 resin. Limit of detection (LOD) and limit of quantification (LOQ) were determined for each phthalate. Phthalate recoveries were evaluated at 3x, 10x and 30x the LOQ, and after storage at -21 degrees C and 21 degrees C. Media were Soxhlet extracted in 10% diethyl ether in hexanes along with an extraction surrogate, di-n-pentyl phthalate-d(4). Gas chromatography/mass spectrometry was performed to quantify the phthalate diesters using di(2-ethylhexyl) phthalate-d(4) as an internal standard. Estimated LODs were 1 microg per sample (BzBP, DEHP, and DnOP), 2 microg per sample (DMP and DBP), and 5 microg per sample (DEP). Mean recoveries under static conditions were 85-104% for DBP, BzBP, DEHP, and DnOP; but <70% for DMP and DEP at 3x and 10x the LOQ. After air was pulled through spiked samples, DMP and DEP recoveries improved to 74-81%. After storage for 62 days, phthalate recovery was better at -21 degrees C than at 21 degrees C. Method accuracy was best for DBP, BzBP, DEHP, and DnOP (range 11-18%), and less so for DMP (28%) and DEP (29%).

Improved analytical methods for measuring urinary phthalate metabolites have resulted in biomarker-based estimates of phthalate daily intake for the general population, but not for occupationally exposed groups. In 2003-2005, we recruited 156 workers from eight industries where materials containing diethyl phthalate (DEP), dibutyl phthalate (DBP), and/or di(2-ethylhexyl) phthalate (DEHP) were used as part of the worker's regular job duties. Phthalate metabolite concentrations measured in the workers' end-shift urine samples were used in a simple pharmacokinetic model to estimate phthalate daily intake. DEHP intake estimates based on three DEHP metabolites combined were 0.6-850 mug/kg/day, with the two highest geometric mean (GM) intakes in polyvinyl chloride (PVC) film manufacturing (17 mug/kg/day) and PVC compounding (12 mug/kg/day). All industries, except phthalate manufacturing, had some workers whose DEHP exposure exceeded the U.S. reference dose (RfD) of 20 mug/kg/day. A few workers also exceeded the DEHP European tolerable daily intake (TDI) of 50 mug/kg/day. DEP intake estimates were 0.5-170 mug/kg/day, with the highest GM in phthalate manufacturing (27 mug/kg/day). DBP intake estimates were 0.1-76 mug/kg/day, with the highest GMs in rubber gasket and in phthalate manufacturing (17 mug/kg/day, each). No DEP or DBP intake estimates exceeded their respective RfDs. The DBP TDI (10 mug/kg/day) was exceeded in three rubber industries and in phthalate manufacturing. These intake estimates are subject to several uncertainties; however, an occupational contribution to phthalate daily intake is clearly indicated in some industries.Journal of Exposure Science and Environmental Epidemiology advance online publication, 16 December 2009; doi:10.1038/jes.2009.62.

BACKGROUND: Polychlorinated biphenyl (PCB) exposures are encountered by the general public by eating contaminated food or living near a previously operating PCB factory or hazardous waste site. PCBs affect the immune, reproductive, nervous, and endocrine systems and are carcinogens. PCBs were banned in the United States in 1977. For public health, it is important to be able to estimate individual risk, especially for vulnerable populations, to monitor the decline in risk over time and to alert the public health community if spikes occur in PCB exposures, by measuring serum PCB levels. The historical decline in PCB exposures cannot be documented within a repeatedly tested general population, since there is no such population. Therefore, our aim was to model serum PCB levels in the US general population over time using published data. METHODS: Models were developed based on 45 publications providing 16,914 background PCB levels in sera collected 1963-2003. Multiple linear regression and exponential decay were used to model the summary PCB levels. RESULTS: Background levels of higher-chlorinated PCBs (five or more chlorines) in sera increased before 1979 and decreased after 1979; a quadratic model was the best fit. However, the exponential decay model explained better the low PCB serum levels still seen in the general population. For lower-chlorinated serum PCBs, no increase or decrease was shown (1.7ppb for all years). CONCLUSIONS: Limitations for both models were lack of repeated measures, non-randomly selected study participants, selected years, concentration on geographic areas centered on PCB waste sites, lack of adjustment for BMI or for laboratory methods. Despite the limitations, this analysis shows that background PCB levels in the general population are still of concern. Future work should focus on uncertainties governing how to interpret the levels with respect to possible long term health effects.