Biomedical subjects

Geary W Olsen

Publications and source records attributed to Geary W Olsen.

14 recordsLinked to original sources

PubMed2006

Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys--probing the determinants of long plasma half-lives.

Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) compounds associated with surface protection product manufactures are distributed globally. The 3-5-year half-lives, reproductive and liver toxicity in animals, and lack of understanding of the factors regulating retention in the body have led to a world-wide public concern for use of these materials. Using a novel physiologically-motivated pharmacokinetic model for renal clearance, perfluoroalkylacid pharmacokinetics in monkeys was successfully described by renal resorption via high efficiency transporters for both intravenous and oral dosing. Intravenous dosing with both PFOA and PFOS in Cynomolgus monkeys produced time course curves consistent with a two-compartment distribution. Extending the PK model for intravenous dosing to examine blood and urine time course data for repeated oral dosing clearly identified the saturable renal resorption. Resorption depends on kinetic factors for transport (T(mC), transport maximum; K(T), transport affinity) and free fraction in plasma (f(plasma)). For PFOA, these parameters were estimated to be 5mg/(h kg) (T(mC)), 0.055 mg/L (K(T)), and 0.02 (f(plasma)). PFOS has longer half-life and had respective values of 13.6 mg/(h kg), 0.023 mg/L, and 0.025. PFOS appeared to have a higher transport capacity and lower affinity than PFOA. Human kinetics indicates even higher resorption efficiency.

Administration, Oral↗

PubMed2006

Comparison of human whole blood, plasma, and serum matrices for the determination of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other fluorochemicals.

Interest in human exposure to perfluorinated acids, including perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHS), perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA) has led to their measurement in whole blood, plasma and serum. Comparison of measurements in these different blood-based matrices, however, has not been rigorously investigated to allow for across-matrix comparisons. This research evaluated concentrations of PFBS, PFHS, PFOS, and PFOA in whole blood collected in heparin (lithium) and ethylenediamine tetraacetic acid (EDTA), plasma samples collected in heparin and EDTA, and serum (from whole blood allowed to clot). Blood samples were collected from 18 voluntary participants employed at 3M Company. Solid phase extraction methods were used for all analytical sample preparations, and analyses were completed using high-pressure liquid chromatography/tandem mass spectrometry methods. Serum concentrations ranged from: limit of quantitation (LOQ, 5 ng/mL) to 25 ng/mL for PFBS; LOQ (5 ng/mL) to 75 ng/mL for PFHS; LOQ (5 ng/mL) to 880 ng/mL for PFOS; and LOQ (5 or 10 ng/mL) to 7320 ng/mL for PFOA. Values less than the LOQ were not included in the statistical analyses of the mean of the ratios of individual values for the matrices. PFBS was not quantifiable in most samples. Serum to plasma ratios for PFHS, PFOS, and PFOA were 1:1 and this ratio was independent of the level of concentrations measured. Serum or plasma to whole blood ratios, regardless of the anticoagulant used, approximated 2:1. The difference between plasma and serum and whole blood corresponded to volume displacement by red blood cells, suggesting that the fluorochemicals are not found intracellularly or attached to the red blood cells.

Adult↗

PubMed2006

The applicability of biomonitoring data for perfluorooctanesulfonate to the environmental public health continuum.

Perfluorooctanesulfonate and its salts (PFOS) are derived from perfluorooctanesulfonyl fluoride, the basic chemical building block for many sulfonyl-based fluorochemicals used as surfactants and for their repellent properties. PFOS is highly persistent in the environment and has a long serum elimination half-life in both animals and humans. PFOS has been detected globally in the environment and in blood serum in various populations throughout the world, with the majority of human sampling done in the United States and Japan. The mechanisms and pathways leading to the presence of PFOS in human blood are not well characterized but likely involve both direct exposures to PFOS or chemicals and materials that can degrade to PFOS, either in the environment or from industrial and commercial uses. In 2000 the 3M Company, a major manufacturer, announced a phaseout of PFOS-related materials. Animal studies indicate that PFOS is well absorbed orally and distributes mainly in blood serum and the liver. Several repeat-dose toxicology studies in animals consistently demonstrated that the liver is the primary target organ. In addition there is a steep dose response for mortality in sexually mature rats and primates as well as in neonatal rats and mice exposed in utero. Several biomonitoring research needs that have been identified on PFOS include additional data from general populations pertaining to other matrices besides blood; matched serum and urine samples from humans and research animals; and comparison of whole blood, serum, and plasma concentrations from the same individuals.

Alkanesulfonic Acids↗

PubMed2005

Historical comparison of perfluorooctanesulfonate, perfluorooctanoate, and other fluorochemicals in human blood.

The purpose of this investigation was to determine whether there has been a change in the human blood concentration of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and five other fluorochemicals since 1974. Blood samples were collected in 1974 (serum) and 1989 (plasma) from volunteer participants of a large community health study. The study included a total of 356 samples (178 from each time period). These samples were analyzed by high-pressure liquid chromatography/tandem mass spectrometry methods. The median 1974 and 1989 fluorochemical concentrations, respectively, were as follows: PFOS, 29.5 ng/mL vs. 34.7 ng/mL; PFOA, 2.3 ng/mL vs. 5.6 ng/mL; perfluorohexanesulfonate (PFHS), 1.6 ng/mL vs. 2.4 ng/mL; and N-ethyl perfluorooctanesulfonamidoacetate (PFOSAA), less than the lower limit of quantitation (LLOQ; 1.6 ng/mL, vs. 3.4 ng/mL). For N-methyl perfluorooctanesulfonamidoacetate (M570), perfluorooctanesulfonamide, and perfluorooctanesulfonamidoacetate, median serum concentrations in both years were less than the LLOQ values (1.0, 1.0, and 2.5 ng/mL, respectively). Statistical analysis of 58 paired samples indicated that serum concentrations of PFOS, PFOSAA, PFOA, PFHS, and M570 were significantly (p < 0.001) higher in 1989 than in 1974. The data from 1989 were then compared with geometric mean fluorochemical concentrations of serum samples collected in 2001 from 108 American Red Cross adult blood donors from the same region. Except for M570, there were no statistically significant (p < 0.05) geometric mean fluorochemical concentration differences between the 1989 and 2001 samples. In conclusion, based on this study population, PFOS and other serum fluorochemical concentrations have increased between 1974 and 1989. Comparison with other regional data collected in 2001 did not suggest a continued increase in concentrations since 1989.

Adult↗

PubMed2005

Worksite influenza immunization programs. Insight into the implementation and cost-benefit.

The most important factors in cost-benefit analyses of worksite influenza immunization programs are vaccine cost and administration, vaccine efficacy, and the assumptions used to calculate lost productivity from worker absenteeism or decreased effectiveness. Based on several models published in the literature, estimates of savings per healthy working adult employee could be anticipated to range between dollars 15 and dollars 50. Variations of this net savings are primarily based on assumptions of productivity estimates of the employee. Efficient large worksite influenza immunization programs are feasible and worthy of employer consideration for economic and employee satisfaction reasons.

Absenteeism↗

PubMed2004

Serum concentrations of perfluorooctanesulfonate and other fluorochemicals in an elderly population from Seattle, Washington.

Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) related-materials have been used as surfactants, paper and packaging treatments, and surface (e.g., carpet, textile, upholstery) protectants. A metabolite, perfluorooctanesulfonate (PFOS, C8F17SO3-), has been identified in the serum and liver of non-occupationally exposed humans and wildlife. Because of its persistence, an important question was whether elderly humans might have higher PFOS concentrations. From a prospective study designed to examine cognitive function in the Seattle (WA) metropolitan area, blood samples were collected from 238 dementia-free subjects (ages 65-96). High-pressure liquid chromatography-electrospray tandem mass spectrometry determined seven fluorochemicals: PFOS; N-ethyl perfluorooctanesulfonamidoacetate; N-methyl perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamide; perfluorooctanoate; and perfluorohexanesulfonate. Serum PFOS concentrations ranged from less than the lower limit of quantitation (3.4 ppb) to 175.0 ppb (geometric mean 31.0 ppb; 95% CI 28.8-33.4). An estimate of the 95% tolerance limit was 84.1 ppb (upper 95% confidence limit 104.0 ppb). Serum PFOS concentrations were slightly lower among the most elderly. There were no significant differences by sex or years residence in Seattle. The distributions of the other fluorochemicals were approximately an order of magnitude lower. Similar to other reported findings of younger adults, the geometric mean serum PFOS concentration in non-occupational adult populations likely approximates 30-40 ppb with 95% of the population's serum PFOS concentrations below 100 ppb.

Age Factors↗

PubMed2004

Characterization of risk for general population exposure to perfluorooctanoate.

Perfluorooctanoate (PFOA), an environmentally and metabolically stable perfluorinated carboxylic acid, has been detected in the serum of children, adults and the elderly from the United States with the upper bound of the 95th percentile estimate in the range of 0.011-0.014 microg/mL (ppm). In this risk characterization, margins of exposure (MOE), which can provide a realistic perspective on potential for human risk, were determined by comparison of general population serum PFOA concentrations with serum concentrations from toxicological studies that are associated with the lower 95% confidence limit of a modeled 10 percent response or incidence level (LBMIC(10)) using USEPA BMDS software. The LBMIC(10) was estimated using surrogate data from other studies or pharmacokinetic relationships if serum PFOA data were not available. Modeled dose-responses (with resulting LBMIC(10) values) included post-natal effects in rats (29 microg/mL), liver-weight increase (23 microg/mL), and body-weight change (60 microg/mL) in rats and monkeys, and incidence of Leydig cell adenoma (125 microg/mL) in rats. MOE values based on the upper bound 95th percentile population serum PFOA concentration were large, ranging from 1600 (liver-weight increase) to 8900 (Leydig cell adenoma). These MOE values represent substantial protection of children, adults, and the elderly.

Adult↗

PubMed2004

Analysis of episodes of care in a perfluorooctanesulfonyl fluoride production facility.

The observed to expected episodes of care experience of 652 employees at a fluorochemical (perfluorooctanesulfonyl fluoride) production facility was compared with 659 film plant (nonfluorochemical) employees at the same site (Decatur, AL). Episodes of care were defined by a hierarchical analysis of health claims data from 1993 through 1998. The age- and sex-adjusted expected number of episodes of care was calculated from the company's U.S. manufacturing workforce. For a priori interests, the observed to expected episodes of care ratios were comparable for fluorochemical and film plant employees for liver tumors or diseases, bladder cancer, thyroid and lipid metabolism disorders, and reproductive, pregnancy, and perinatal disorders and higher for biliary tract disorders and cystitis recurrence. Non-a priori associations among the fluorochemical plant workers included benign colon polyps, malignant colorectal tumors, and malignant melanoma.

Adult↗

PubMed2003

Human donor liver and serum concentrations of perfluorooctanesulfonate and other perfluorochemicals.

Perfluorooctanesulfonate (PFOS, CaF17SO3-) has been identified in the serum of nonoccupationally exposed humans and in serum and liver tissue in wildlife. The purpose of this investigation was to determine whether PFOS liver concentrations in humans are comparable to the approximate 30 ng/mL average serum concentrations reported in nonoccupationally exposed subjects. Thirty-one donors (16 male and 15 female, age range 5-74) provided serum and/or liver samples for analysis of PFOS and three other fluorochemicals: perfluorosulfonamide (PFOSA, C8F17SO2NH2), perfluorooctanoate (PFOA, C7F15CO2-), and perfluorohexanesulfonate (PFHxS, C6F13SO3-). Both sera and liver samples were extracted by ion-pair extraction and quantitatively assayed using high-performance liquid chromatography electrospray tandem mass spectrometry. Liver PFOS concentrations ranged from <4.5 ng/g (limit of quantitation, LOQ)to 57.0 ng/g. Serum PFOS concentrations ranged from <6.1 ng/mL (LOQ) to 58.3 ng/mL. Among the 23 paired samples, the mean liver to serum ratio was 1.3:1 (95% confidence interval 0.9:1-1.7:1). This liver to serum ratio is comparable to that reported in a toxicological study of cynomolgus monkeys, which had liver and serum concentrations 2-3 orders of magnitude higher than observed in these human donors. This information may be useful in human risk characterization for PFOS. Liver to serum ratios were not estimated for PFOA, PFHxS, and PFOSA as 90% of the human donor liver samples were determined to be less than the LOQ.

Adolescent↗

PubMed2003

Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations.

Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) is used to create applications for surfactants and paper, packaging, and surface (e.g., carpets, textiles) protectants. Such POSF-based products or their residuals may degrade or metabolize to PFOS (C8F17SO3-). PFOS concentrates in liver and serum and results in hypolipidemia as an early effect of cumulative dosages. Male and female employees of two perfluorooctanyl-manufacturing locations (Antwerp, Belgium and Decatur, Alabama) participated in a periodic medical surveillance program that included hematology, clinical chemistry, thyroid hormone, and urinalysis testing. Serum concentrations of PFOS and perfluorooctanoate (PFOA, C7F15CO2-, used as a fluoropolymer emulsifier) were measured via mass spectrometry methods. The mean serum PFOS and PFOA concentrations for 263 Decatur employees were 1.32 parts per million (ppm; geometric mean 0.91, range 0.06-10.06 ppm) and 1.78 ppm (geometric mean 1.13, range 0.04-12.70 ppm), respectively. Mean concentrations were approximately 50% lower among 255 Antwerp workers. Adjusting for potential confounding factors, there were no substantial changes in hematological, lipid, hepatic, thyroid, or urinary parameters consistent with the known toxicological effects of PFOS or PFOA in cross-sectional or longitudinal analyses of the workers' measured serum fluorochemical concentrations.

Alkaline Phosphatase↗

PubMed2003

Perfluorooctanesulfonate and other fluorochemicals in the serum of American Red Cross adult blood donors.

Perfluorooctanesulfonyl fluoride-based products have included surfactants, paper and packaging treatments, and surface protectants (e.g., for carpet, upholstery, textile). Depending on the specific functional derivatization or degree of polymerization, such products may degrade or metabolize, to an undetermined degree, to perfluorooctanesulfonate (PFOS), a stable and persistent end product that has the potential to bioaccumulate. In this investigation, a total of 645 adult donor serum samples from six American Red Cross blood collection centers were analyzed for PFOS and six other fluorochemicals using HPLC-electrospray tandem mass spectrometry. PFOS concentrations ranged from the lower limit of quantitation of 4.1 ppb to 1656.0 ppb with a geometric mean of 34.9 ppb [95% confidence interval (CI), 33.3-36.5]. The geometric mean was higher among males (37.8 ppb; 95% CI, 35.5-40.3) than among females (31.3 ppb; 95% CI, 30.0-34.3). No substantial difference was observed with age. The estimate of the 95% tolerance limit of PFOS was 88.5 ppb (upper limit of 95% CI, 100.0 ppb). The measures of central tendency for the other fluorochemicals (N-ethyl perfluorooctanesulfonamidoacetate, N-methyl perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamide, perfluorooctanoate, and perfluorohexanesulfonate) were approximately an order of magnitude lower than PFOS. Because serum PFOS concentrations correlate with cumulative human exposure, this information can be useful for risk characterization.

Adult↗

PubMed2002

Subchronic toxicity studies on perfluorooctanesulfonate potassium salt in cynomolgus monkeys.

This study was conducted to determine the earliest measurable response of primates to low-level perfluorooctanesulfonate (PFOS) exposure and to provide information to reduce uncertainty in human health risk assessment. Groups of male and female monkeys received 0, 0.03, 0.15, or 0.75 mg/kg/day potassium PFOS orally for 182 days. Recovery animals from each group, except the 0.03 mg/kg/day dose group, were monitored for one year after treatment. Significant adverse effects occurred only in the 0.75 mg/kg/day dose group and included compound-related mortality in 2 of 6 male monkeys, decreased body weights, increased liver weights, lowered serum total cholesterol, lowered triiodothyronine concentrations (without evidence of hypothyroidism), and lowered estradiol levels. Decreased serum total cholesterol occurred in the 0.75 mg/kg/day dose group at serum PFOS levels > 100 ppm. Hepatocellular hypertrophy and lipid vacuolation were present at term in the 0.75 mg/kg/day dose group. No peroxisomal (palmitoyl CoA oxidase) or cell proliferation (proliferating cell nuclear antigen immunohistochemistry) was detected. Complete reversal of clinical and hepatic effects and significant decreases in serum and liver PFOS occurred within 211 days posttreatment. Liver-to-serum PFOS ratios were comparable in all dose groups, with a range of 1:1 to 2:1. Serum concentrations associated with no adverse effects (0.15 mg/kg/day) were 82.6 +/- 25.2 ppm for males and 66.8 +/- 10.8 ppm for females. Comparison of serum PFOS concentrations associated with no adverse effect in this study to those reported in human blood samples (0.028 +/- 0.014 ppm) indicated an adequate margin of safety.

Administration, Oral↗

PubMedDate not supplied

The toxicology of perfluorooctanoate.

PFOA is a peroxisome proliferator (PPAR agonist) and exerts morphological and biochemical effects characteristic of PPAR agonists. These effects include increased beta-oxidation of fatty acids, increases in several cytochrome P-450 (CYP450)-mediated reactions, and inhibition of the secretion of very low-density lipoproteins and cholesterol from the liver. These effects on lipid metabolism and transport result in a reduction of cholesterol and triglycerides in serum and an accumulation of lipids in the liver. The triad of tumors observed (liver, Leydig cell, and pancreatic acinar-cell) is typical of many PPAR agonists and is believed to involve nongenotoxic mechanisms. The hepatocellular tumors observed in rats are likely to have been the result of the activation of the peroxisome proliferator activated receptor alpha (PPARalpha). The tumors observed in the testis (Leydig-cell) have been hypothesized to be associated with an increased level of serum estradiol in concert with testicular growth factors. The mechanism responsible for the acinar-cell tumors of the pancreas in rats remains the subject of active investigation. The mechanism resulting in the hepatocellular tumors in rats (PPARalpha activation) is not likely to be relevant to humans. Similarly, the proposed mechanism for Leydig-cell tumor formation is of questionable relevance to humans. Acinar tumors of the pancreas are rare in humans, and the relevance of the these tumors, as found in rats, to humans is uncertain. Epidemiological investigations and medical surveillance of occupationally exposed workers have not found consistent associations between PFOA exposure and adverse health effects.

Animals↗

PubMedDate not supplied

An occupational exposure assessment of a perfluorooctanesulfonyl fluoride production site: biomonitoring.

This investigation randomly sampled a fluorochemical manufacturing employee population to determine the distribution of serum fluorochemical levels according to employees' jobs and work areas. Previous analyses of medical surveillance data have not shown significant associations between fluorochemical production employees' clinical chemistry and hematology tests and their serum PFOS and perfluorooctanoate (PFOA, C(7)F(15)COO(-)) concentrations, but may have been subject to nonparticipation bias. A random sample of the on-site film plant employee population, where fluorochemicals are not produced, determined their serum concentrations also. Of the 232 employees randomly selected for serum sampling, 186 (80%) employees participated (n=126 chemical plant; n=60 film plant). Sera samples were extracted using an ion-pairing extraction procedure and were quantitatively analyzed for seven fluorochemicals using high-pressure liquid chromatography electrospray tandem mass spectrometry methods. Geometric means (in parts per million) and 95% confidence intervals (in parentheses) of the random sample of 126 chemical plant employees were: PFOS 0.941 (0.787-1.126); PFOA 0.899 (0.722-1.120); perfluorohexanesulfonate 0.180 (0.145-0.223); N-ethyl perfluorooctanesulfonamidoacetate 0.008 (0.006-0.011); N-methyl perfluorooctanesulfonamidoacetate 0.081 (0.067-0.098); perfluorooctanesulfonamide 0.013 (0.009-0.018); and perfluorooctanesulfonamidoacetate 0.022 (0.018-0.029). These geometric means were approximately one order of magnitude higher than those observed for the film plant employees.

Alkanesulfonic Acids↗