Gunilla Sandborgh-Englund

Pharmacokinetics of Triclosan Following Oral Ingestion in Humans

The number of personal hygiene products containing triclosan has increased rapidly during the last decade, and triclosan is one of the most common antibacterial compounds used in dentifrices today. However, the extent of triclosan exposure has not yet been well described. The potential risks of generating triclosan-resistant pathogenic microorganisms or of the selection of resistant strains are some areas of concern. The aim of the present study was to (1) obtain information on baseline levels of triclosan in plasma and urine, and (2) study the pharmacokinetic pattern of triclosan after a single-dose intake. Ten healthy volunteers were exposed to a single oral dose of 4 mg triclosan by swallowing an oral mouthwash solution. Triclosan in plasma and urine was followed before and up to 8 d after exposure. Triclosan levels in plasma increased rapidly, with a maximum concentration within 1 to 3 h, and the terminal plasma half-life was 21 h. The major fraction was excreted within the first 24 h. The accumulated urinary excretion varied between the subjects, with 24 to 83% of the oral dose being excreted during the first 4 d after exposure. In conclusion, triclosan appears to be readily absorbed from the gastrointestinal tract and has a rapid turnover in humans. The high lipid solubility of the substance gives rise to questions regarding distribution properties and accumulation. The findings of the present study form a basis for greater understanding of the toxicokinetic properties of triclosan in humans.

The influence of age and gender on triclosan concentrations in Australian human blood serum

The bactericide triclosan has found wide-spread use in e.g. soaps, deodorants and toothpastes. Recent in vitro and in vivo studies indicate that triclosan might exert adverse effects in humans. Triclosan has previously been shown to be present in human plasma and milk at concentrations that are well correlated to the use of personal care products containing triclosan. In this study we investigated the influence of age, gender, and the region of residence on triclosan concentrations in pooled samples of Australian human blood serum. The results showed no influence of region of residence on the concentrations of triclosan. There was a small but significant influence of age and gender on the serum triclosan concentrations, which were higher in males than in females, and highest in the group of 31-45 year old males and females. However, overall there was a lack of pronounced differences in the triclosan concentrations within the dataset, which suggests that the exposure to triclosan among different groups of the Australian population is relatively homogenous. A selection of the dataset was compared with previous measurements of triclosan concentrations in human plasma from Sweden, where the use of triclosan is expected to be low due to consumer advisories. The triclosan concentrations were a factor of 2 higher in Australian serum than in Swedish plasma.

Mercury in Biological Fluids after Amalgam Removal

Dental amalgam is the major source of inorganic mercury (Hg) exposure in the general population. The objective of the present study was to obtain data on changes in Hg levels in blood, plasma, and urine following removal of all amalgam fillings during one dental session in 12 healthy subjects. The mean number of amalgam surfaces was 18 (range, 13 to 34). Frequent blood sampling and 24-hour urine collections were performed up to 115 days after amalgam removal, and in eight subjects additional samples of plasma and urine were collected up to three years after amalgam removal. A transient increase of Hg concentrations in blood and plasma was observed within 48 hours after amalgam removal. In plasma, the peak concentrations significantly exceeded the pre-removal plasma Hg levels by, on average, 32% (1.3 nmol/L; range, 0.1 to 4.2). No increase in the urinary Hg excretion rate was apparent after amalgam removal. An exponential decline of Hg was seen in all media. Sixty days after the amalgam removal, the Hg levels in blood, plasma, and urine had declined to approximately 60% of the pre-removal levels. In seven subjects, who were followed for up to three years, the half-lives of Hg in plasma and urine were calculated. In plasma, a bi-exponential model was applied, and the half-life was estimated at median 88 days (range, 21 to 121). The kinetics of Hg in urine (nmol/24 hrs) fit a mono-exponential model with a median half-life of 46 days (range, 35 to 67). It is concluded that the process of removing amalgam fillings can have a considerable impact on Hg levels in biological fluids. After removal, there was a considerable decline in the Hg levels of blood, plasma, and urine, which slowly approached those of subjects without any history of amalgam fillings.

Digitization of simulated clinical dental impressions: Virtual three-dimensional analysis of exactness

OBJECTIVES To compare the exactness of simulated clinical impressions and stone replicas of crown preparations, using digitization and virtual three-dimensional analysis. METHODS Three master dies (mandibular incisor, canine and molar) were prepared for full crowns, mounted in full dental arches in a plane line articulator. Eight impressions were taken using an experimental monophase vinyl polysiloxane-based material. Stone replicas were poured in type IV stone (Vel-Mix Stone; Kerr). The master dies and the stone replicas were digitized in a touch-probe scanner (Procera) Forte; Nobel Biocare AB) and the impressions in a laser scanner (D250, 3Shape A/S), to create virtual models. The resulting point-clouds from the digitization of the master dies were used as CAD-Reference-Models (CRM). Discrepancies between the points in the pointclouds and the corresponding CRM were measured by a matching-software (CopyCAD 6.504 SP2; Delcam Plc). The distribution of the discrepancies was analyzed and depicted on color-difference maps. RESULTS The discrepancies of the digitized impressions and the stone replicas compared to the CRM were of similar size with a mean+/-SD within 40microm, with the exception of two of the digitized molar impressions. The precision of the digitized impressions and stone replicas did not differ significantly (F=4.2; p=0.053). However, the shape affected the digitization (F=5.4; p=0.013) and the interaction effect of shape and digitization source (impression or stone replica) was pronounced (F=28; p<0.0001). The reliability was high for both digitization methods, evaluated by repeated digitizations. SIGNIFICANCE The exactness of the digitized impressions varied with shape. Both impressions and stone replicas can be digitized repeatedly with a high reliability.

Cancer and mortality among users and nonusers of snus.

Scandinavian moist snuff (snus) is claimed to be a safer alternative to smoking. We aimed to quantify cancer incidence among male snus users and to shed light on the net health outcome by studying their overall mortality. A cohort, comprised of 9,976 men who participated in a population‐based survey, was compiled in 1973–74. Follow‐up until January 31, 2002, was accomplished through record‐linkages with nation‐wide and essentially complete registers of demographics, cancer and causes of deaths. Adjusted relative risks among exposed relative to unexposed men were estimated using Cox proportional hazards regression. The cohort members contributed more than 220,000 person‐years at risk for cancer. A statistically significant increase in the incidence of the combined category of oral and pharyngeal cancer among daily users of snus (incidence rate ratio 3.1, 95% confidence interval 1.5–6.6) was found. Overall mortality was also slightly increased (hazard ratio 1.10, 95% confidence interval 1.01–1.21). Although the combined previous literature on snus and oral cancer weigh toward no association, this population‐based prospective study provided suggestive evidence of snus‐related risks that cannot be lightly ignored.

Longevity of posterior resin composite restorations in adults - A systematic review

OBJECTIVE To conduct a systematic review of the literature on the longevity of posterior resin composite restorations in adults. MATERIAL AND METHODS A systematic literature search was conducted according to pre-determined criteria for inclusion and exclusion. The studies selected were prospective clinical trials with a minimum follow-up time of 4 years, 40 restorations per experimental group and an annual attrition rate of less than 5%. Initially, abstracts and full-text articles were assessed independently and the assessment was subsequently agreed on by five reviewers. The methodological quality of the studies was assessed according to the Swedish Council on Health Technology Assessment (SBU) standard checklist for determining the extent to which studies meet basic quality criteria. RESULTS In all, the literature search identified 4275 abstracts and 93 articles were read in full-text. There were eighteen studies which met the criteria for inclusion, eight of which were included in the analysis. There were 80 failures of restorations with a total follow-up time at risk for failure of 62,030 months. The overall incidence rate for all causes of failure was 1.55 lost restorations per 100 restoration years. The most common biological reason for failure (a total of 31 restorations) was secondary caries, with or without fracture of the restoration. The quality of the evidence was low. CONCLUSIONS In an efficacy setting, the overall survival proportion of posterior resin composite restorations is high. The major reasons for failure are secondary caries and restoration fracture which supports the importance of adequate follow-up time. CLINICAL SIGNIFICANCE The overall survival proportion of posterior composite restorations was high, but the results cannot be extrapolated to an effectiveness setting. The importance of adequate follow-up time is supported by the finding that secondary caries often occurred after 3 years or later.

Computer aided analysis of digitized dental stone replicas by dental CAD/CAM technology

OBJECTIVES To determine the reproducibility of digitized dental stone replicas compared to the master model and the reliability of the computer aided analysis. METHODS Four master dies, prepared for complete crowns were fabricated in presintered yttria-stabilized tetragonal zirconia (Y-TZP). Eight vinyl polysiloxane impressions (PROVIL novo; Heraeus Kulzer) were taken of each die and stone replicas were poured in type IV stone (Vel-Mix Stone; Kerr). The master dies and the stone replicas were digitized in a touch-probe scanner (Procera Forte; Nobel Biocare AB), to create triangulated surface-models. The point-cloud from the first of the repeated digitizations of each master die was used as CAD-reference-models (CRM). Discrepancies between the points in the triangulated surface-models and the corresponding CRM were measured by a matching-software (CopyCAD 6.504 SP2; Delcam Plc). The distribution of the discrepancies was analyzed and presented in color-difference-maps. RESULTS The precision of the measuring method, presented as the repeatability coefficient, ranged between 7 and 16 microm (entire surface), whereas the analysis of the stone replicas revealed a precision (repeatability coefficient) ranging from 19 to 26 microm. The accuracy of the replica to master (the mean discrepancy) ranged from 0.5 to 2.0 microm (95% confidence interval 1.5-2.9 microm). SIGNIFICANCE The greatest precision of the measurement was seen in the jacket surface of the die. The size of the stone replicas varied and the repeatability coefficient was on average 15 microm (2-25 microm) greater for the replica-to-master alignment than the repeated digitizations of the master.

Human Exposure to Triclosan via Toothpaste does not change CYP3A4 Activity or Plasma Concentrations of Thyroid Hormones

Triclosan is an antibacterial compound commonly used in cosmetics and personal care products for everyday use. As previously shown, triclosan is found in the plasma, urine and milk from large parts of different human populations. Recent studies have revealed that triclosan is able to activate the human pregnane X receptor in vitro and thus possibly affecting metabolism of drugs in humans via the induction of CYP3A4. Besides, triclosan has been shown to affect thyroid hormonal levels in rats in vivo. In the present study, we investigated if an everyday exposure to triclosan via triclosan-containing toothpaste for 14 days in 12 adult humans caused an increase in plasma 4beta-hydroxycholesterol, indicative of CYP3A4 induction, and/or alterations in thyroid hormonal status. The plasma triclosan concentrations increased from 0.009-0.81 ng/g to 26-296 ng/g (ranges) upon exposure. Despite this, there were no significant changes in plasma levels of either plasma 4beta-hydroxycholesterol or thyroid hormones during the exposure. This indicates that the normal use of triclosan-containing toothpaste is not likely to alter metabolism of drugs via CYP3A4 induction or cause adverse events because of thyroid disturbances in humans.

MERCURY EXPOSURE IN UTERO AND DURING INFANCY

Mercury in blood samples was speciated from mothers and their infants up to 2 mo after delivery. There were significant correlations between umbilical cord blood and maternal blood for methylmercury (MeHg) and inorganic mercury (I-Hg) levels. The MeHg levels in cord blood were significantly higher than in maternal blood, while I-Hg levels were about the same. The maternal MeHg and I-Hg levels remained stable during the sampling period, whereas the MeHg concentration in infant blood decreased more than 45% between the 72-h and 2 mo sampling times. The I-Hg levels in infant blood were low at birth, and remained low during the sampling period. The results of the present study do not support I-Hg absorption through milk as a significant source of exposure. However, the number of observations is small, and a larger study is warranted in order to verify the data.

Mercury Uptake and Kinetics after Ingestion of Dental Amalgam

The aim of the present study was to investigate the G-I uptake of mercury (Hg) after intake of a single dose of amalgam-Hg, followed by pharmacokinetic analysis of the data. Eleven volunteers without amalgam fillings ingested 1.00 g amalgam powder. Hg in plasma vs. time was analyzed with a two-compartment model by means of mixed-effects modeling. A fraction of the absorption rate of Hg to the central compartment was inversely proportional to the plasma ferritin levels. The population mean half-life of the terminal phase of Hg in plasma was 37 days, with a considerable standard deviation in the population. The absorbed fraction of the administered dose was estimated to be about 0.04%. It is concluded that the G-I uptake of Hg is of quantitative importance during dental treatment.