A Multi-Individual Pharmacokinetic Model Framework for Interpreting Time Trends of Persistent Chemicals in Human Populations: Application to a Postban Situation

Ba c k g r o u n d: Human milk and blood are monitored to detect time trends of persistent organic pollutants (POPs) in humans. It is current practice to use log-linear regression to fit time series of averaged cross-sectional biomonitoring data, here referred to as cross-sectional trend data (CSTD). O b j e c t i v e: The goals of our study are to clarify the interpretation of half-lives derived from fitting exponential functions to declining CSTD and to provide a method of estimating human elimina-tion half-lives from CSTD collected in a postban situation. M e t h o d s: We developed a multi-individual pharmacokinetic model framework and present analytical solutions for a postban period. For this case, the framework quantitatively describes the relationships among the half-life for reduction of body burdens of POPs derived from CSTD, the half-life describing decline in daily intake, and the half-life of elimination from the human body. R e s u l t s: The half-life derived from exponential fitting of CSTD collected under postban conditions describes the exposure trend and is independent of human elimination kinetics. We use a case study of DDT (dichlorodiphenyltrichloroethane) to show that CSTD can be combined with exposure data obtained from total diet studies to estimate elimination kinetics of POPs for humans under background exposure conditions. C o n c l u s i o n s: CSTD provide quantitative information about trends in human exposure and can be combined with exposure studies to estimate elimination kinetics. The full utility of these data has not been exploited so far. An efficient and informative monitoring strategy for banned POPs in humans would coordinate sampling of consistent sets of CSTD from young adults with total diet studies.ISSN:1552-9924ISSN:0091-676

Twenty-four hours secretion pattern of serum estradiol in healthy prepubertal and pubertal boys as determined by a validated ultra-sensitive extraction RIA

<p>Abstract</p> <p>Background</p> <p>The role of estrogens in male physiology has become evident. However, clinically useful normative data for estradiol secretion in boys has not previously been established due to the insensitivity of current methods used in clinical routine. By use of a validated ultra-sensitive extraction RIA, our aim was to establish normative data from a group consisting of healthy boys in prepuberty and during pubertal development.</p> <p>Methods</p> <p>Sixty-two 24-hours serum profiles (6 samples/24 hours) were obtained from 44 healthy boys (ages; 7.2–18.6 years) during their pubertal development, classified into five stages: prepuberty (testis, 1–2 mL), early (testis, 3–6 mL), mid (testis, 8–12 mL), late-1 (testis,15–25 mL, not reached final height) and late-2 (testis,15–25 mL, reached final height). Serum estradiol was determined by an ultra- sensitive extraction radioimmunoassay with detection limit 4 pmol/L and functional sensitivity 6 pmol/L.</p> <p>Results</p> <p>Mean estradiol concentrations during 24-hours secretion increased from prepuberty (median: <4 (5–95 percentiles: <4 – 7) pmol/L) to early puberty (6 (<4 – 12 pmol/L) but then remained relatively constant until a marked increase between mid-puberty (8 (4 – 17) pmol/L) and late-1 (21 (12 – 37) pmol/L) puberty, followed by a slower increase until late-2 puberty (32 (20 – 47) pmol/L). The diurnal rhythm of serum estradiol was non-measurable in pre- and early puberty, but discerned in mid-puberty, and become evident in late pubertal stages with peak values at 0600 to 1000 h.</p> <p>Conclusion</p> <p>With the use of an ultra-sensitive extraction RIA, we have provided clinically useful normative data for estradiol secretion in boys.</p

Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6–9 Years of age : a cross-sectional analysis within the C8 health project

Background: Exposure to some perfluoroalkyl substances (PFAS), such as perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA), may alter levels of sex hormones and insulin-like growth factor-1 (IGF-1) in animals. Human studies on this topic are scarce and none have been conducted in young children. Objectives: To investigate the relationship between levels of PFAS and estradiol, total testosterone and IGF-1 in 2,292 children (aged 6-9 years) from the C8 Health Project living near a chemical plant in the Mid-Ohio Valley (USA) with local contamination from PFOA. Methods: Serum samples were collected in 2005-2006 and analyzed for PFAS, sex hormones and IGF-1. Results from regression models were expressed as the adjusted percentage difference (95% CI) per sex-specific interquartile range (IQR) increment of each PFAS serum concentration. Analyses by PFAS quartiles were also conducted. Results: Median concentrations of PFHxS, PFOA, PFOS, and PFNA were 8, 35, 22, and 1.7 ng/mL in boys and 7, 30, 21, and 1.7 ng/mL in girls. In boys, PFOA concentrations were significantly associated with testosterone levels (-4.9% [-8.7, -0.8%]); PFOS with estradiol (-4.0% [-7.7, -0.1%]), testosterone (-5.8% [-9.4, -2.0%]), and IGF-1 (-5.9% [-8.3, -3.3%]); and PFNA with IGF-1 (-3.5% [-6.0, -1.0%]). In girls, significant associations were found between PFOS and testosterone (-6.6% [-10.1, -2.8%]) and IGF-1 (-5.6% [-8.2, -2.9%]); and PFNA and IGF-1 (-3.8% [-6.4, -1.2%]). In both sexes, the magnitudes of the associations decreased monotonically across quartiles for testosterone and PFOS, and for IGF-1 and both PFOS and PFNA. Conclusions: To our knowledge, this is the first study suggesting that PFAS are associated with lowe

Immune cell counts and risks of respiratory infections among infants exposed pre- and postnatally to organochlorine compounds: a prospective study

<p>Abstract</p> <p>Background</p> <p>Early-life chemical exposure may influence immune system development, subsequently affecting child health. We investigated immunomodulatory potentials of polychlorinated biphenyls (PCBs) and <it>p,p'</it>-DDE in infants.</p> <p>Methods</p> <p>Prenatal exposure to PCBs and <it>p,p'</it>-DDE was estimated from maternal serum concentrations during pregnancy. Postnatal exposure was calculated from concentrations of the compounds in mother's milk, total number of nursing days, and percentage of full nursing each week during the 3 month nursing period. Number and types of infections among infants were registered by the mothers (N = 190). White blood cell counts (N = 86) and lymphocyte subsets (N = 52) were analyzed in a subgroup of infants at 3 months of age.</p> <p>Results</p> <p>Infants with the highest prenatal exposure to PCB congeners CB-28, CB-52 and CB-101 had an increased risk of respiratory infection during the study period. In contrast, the infection odds ratios (ORs) were highest among infants with the lowest prenatal mono-<it>ortho </it>PCB (CB-105, CB-118, CB-156, CB-167) and di-<it>ortho </it>PCB (CB-138, CB-153, CB-180) exposure, and postnatal mono- and di-<it>ortho </it>PCB, and <it>p,p'</it>-DDE exposure. Similar results were found for pre- and postnatal CB-153 exposure, a good marker for total PCB exposure. Altogether, a negative relationship was indicated between infections and total organochlorine compound exposure during the whole pre- and postnatal period. Prenatal exposure to CB-28, CB-52 and CB-101 was positively associated with numbers of lymphocytes and monocytes in infants 3 months after delivery. Prenatal exposure to <it>p,p'</it>-DDE was negatively associated with the percentage of eosinophils. No significant associations were found between PCB and <it>p,p'</it>-DDE exposure and numbers/percentages of lymphocyte subsets, after adjustment for potential confounders.</p> <p>Conclusion</p> <p>This hypothesis generating study suggests that background exposure to PCBs and <it>p,p'</it>-DDE early in life modulate immune system development. Strong correlations between mono- and di-<it>ortho </it>PCBs, and <it>p,p'</it>-DDE exposures make it difficult to identify the most important contributor to the suggested immunomodulation, and to separate effects due to pre- and postnatal exposure. The suggested PCB and <it>p,p'</it>-DDE modulation of infection risks may have consequences for the health development during childhood, since respiratory infections early in life may be risk factors for asthma and middle ear infections.</p

Risk assessment of persistent, chlorinated and brominated environmental pollutants in food

This report documents the scientific basis for the Swedish National Food Administration’s (NFA) risk assessment of persistent organic halogenated environmental contaminants in food. The risk assessment is part of the work associated with a revision of NFA’s advice to consumers with regard to fish contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). PCBs are industrial chemicals which have been prohibited in most countries of the world for many years. Levels of PCBs in the environment have dropped since the 1970’s. PCDD/Fs (dioxins) are compounds that are produced unintentionally during combustion processes and when certain chemicals are produced. Great emphasis has been placed on minimizing the presence of these contaminants in the environment. NFA’s risk assessment focus mainly on PCDD/F (dioxins) and PCBs, even though there are many other organic halogenated environmental contaminants in food. Current knowledge indicates that PCBs and dioxins are the halogenated compounds that have the largest potential to cause negative health effects among the human population. Exposure to DDT compounds in Sweden is low as compared with the levels that the World Health Organization (WHO) considers to be safe. Extensive international epidemiological research on the potential health risks of DDT compounds suggest that the compounds are not a significant health risk in Sweden. Current knowledge about brominated flame retardant compounds suggest that there is enough of a margin between exposure from food in Sweden and the levels at which there is an increased risk for health effects in animal experiments