Search PubMedSearch

Biomedical subjects

J M Christensen

Publications and source records attributed to J M Christensen.

At least 19 recordsLinked to original sources

Human exposure to toxic metals: factors influencing interpretation of biomonitoring results.

An important approach to assessment of risk from environmental and occupational exposures is biomonitoring which provides an estimate of the total dose absorbed and gives indirect access to determination of target site concentrations. It is also a tool for assessing residual exposure, when respiratory protection is used. The interest in biological effects from toxic metals has increased during the last decades, as large amounts of metals have been released into industrial areas, and it is estimated that approximately 150,000 Danish workers are exposed to various metals. Since biomonitoring results play an important role in decision-making regarding great health and economic impact, understanding the factors influencing validity of such data is essential. In the present survey, the toxic elements arsenic, cadmium, chromium, cobalt, lead and nickel are used as examples to illustrate the disturbing factors in the interpretation of biomonitoring results. The aim of collecting samples is to obtain a small and representative sample of subjects or of a subpopulation being investigated for specific purposes, e.g. the pollution at Mundelstrup, where arsenic exposure of inhabitants and workers engaged in removing contaminated soil was monitored. As exposures vary over time and between subjects, it should be recognized that sampling as well as analytical variations contribute both to bias and random errors. Also biomonitoring data are a function of demographic, lifestyle and geographic factors. Therefore, stratified sampling designs are of the utmost importance. Half-lives play an important role. For short half-lives below 10 h, no decision can be made on long-term exposure if only one urine sample has been taken. For arsenic, cobalt, chromium and nickel in urine measured at the end of a workweek (t1/2: 20-100 h), 2-3 samples should be taken to monitor a single worker, and the results should be interpreted from the average of the results. For groups of workers, it is recommended that results from at least 5-10 workers be used to obtain a useful group mean value. In general, pharmacokinetics modelling contributes to information on sampling time and sampling size. Intake of cobalt in mineral tablets containing soluble cobalt compounds was a factor with a large influence on blood and urinary levels. Age and gender influence the blood and urine concentrations of arsenic, cadmium, cobalt and lead, e.g. B-Pb in females is 20-30% lower than B-Pb in males.(ABSTRACT TRUNCATED AT 400 WORDS)

Environmental Exposure

Estimation of reference values for urinary 1-hydroxypyrene and alpha-naphthol in Danish workers.

In order to assess environmentally and occupationally related exposures to PAH compounds it is essential to have reference or normal values in human body fluids. The establishment of reliable reference intervals is an absolute pre-requisite in determining relationships between internal PAH exposure in humans and health effects in occupationally exposed workers. In this context the estimation of the biological level of PAH metabolites in urine from reference populations has become increasingly important in the field of environmental and occupational toxicology. The present study describes the calculation of tentative reference values for urinary 1-hydroxypyrene on the basis of two reference populations and for urinary alpha-naphthol on the basis of one reference population in accordance with IFCC recommendations. The study subjects were 115 healthy male workers occupationally exposed to PAH at low levels and 121 reference subjects non-occupationally exposed to PAH. Tentative reference values for urinary 1-hydroxypyrene were estimated. In addition, 236 healthy male workers were used to estimate tentative reference values for urinary alpha-naphthol. The reference populations were described by distribution free one-sided tolerance intervals. The 95% one-sided tolerance limit calculated for 1-hydroxypyrene in urine was 0.053 mumol/mol creatinine for non-occupationally exposed individuals and 0.169 mumol/mol creatinine for low level PAH exposed workers, with the coverage interval (95 +/- 4.5) percent at a probability of 0.95. Thus, the probability was 0.975 that the tolerance interval included at least 90.5% of the distribution. In addition, the probability was 0.025 that the tolerance interval included > 99.5% of the population. The tolerance interval for alpha-naphthol in urine was 5.665 mumol/mol creatinine with the coverage interval (95 +/- 4.5) percent at a probability of 0.95.

Air Pollutants, Occupational

Assessment of long-term styrene exposure: a comparative study of a logbook method and biological monitoring.

In a recent joint European research project "Biomonitoring of human populations exposed to genotoxic environmental chemicals: biomonitoring of styrene exposed individuals", a logbook method for assessment of long-term styrene exposure was applied in two Danish factories manufacturing glass fibre-reinforced polyester. The method was based on work process identification, assignment of work process concentrations and logbook keeping. Measures of exposure calculated by this method were compared with results from simultaneous measurements of styrene in blood and the metabolites mandelic acid and phenylglyoxylic acid in urine. Correlations were comparable with those obtained by use of personal samplers as published in the literature. Styrene in blood, however, only correlated with logbook concentrations at the time of sampling. Exposures were moderate to low. Mean personal 8-h time-weighted average concentration (8hTWAC) was 76 mg/m3 styrene (SD 54 mg/m3, range 2-230 mg/m3). The Danish 8hTWAC threshold limit value for styrene in air, 105 mg/m3 (25 ppm), was exceeded on 17% of personal days. The summed urinary metabolites, mandelic acid and phenylglyoxylic acid, had a mean personal value of 138 mg/g creatinine (SD 84 mg/g creatinine) on the day of sampling. Blood styrene mean value was 129 micrograms/l (SD 74 micrograms/l, range 66-358 micrograms/l). It is concluded that the logbook method offers a technique for testing whether measurements are performed on representative days and may be recommended as a tool supplementary to biological monitoring in the assessment of long-term exposure.

Adult

A 1982-1992 surveillance programme on Danish pottery painters. Biological levels and health effects following exposure to soluble or insoluble cobalt compounds in cobalt blue dyes.

This paper provides a short overview of cobalt-related diseases with particular reference to the potential carcinogenicity of cobalt compounds, and a review of a 10-year surveillance programme on plate painters exposed to cobalt in two Danish porcelain factories. Clinical experience and epidemiological studies have demonstrated that cobalt exposure may lead to severely impaired lung function, i.e. hard metal lung disease and occupational cobalt-related asthma, contact dermatitis and cardiovascular effects. However, the evidence for the carcinogenicity of cobalt and cobalt compounds is considered inadequate (IARC, 1991). Most frequently, exposure to cobalt occurs simultaneously with exposure to other elements known to pose a health risk, (e.g. nickel, arsenic, chromium, tungsten). The importance of cobalt as sole causal agent in hard metal lung diseases, cardiomyopathy and cancer are still a matter of controversy. In the two Danish porcelain factories, cobalt blue underglaze dyes have been used since 1888. In contrast to the exposure experience of hard metal factories, the exposure of plate painters occurs with only low trace levels of other potentially harmful compounds such as the carcinogenic metals nickel, arsenic and chromium. Consequently, the nearly-pure cobalt exposure makes the plate painters an attractive group for studies on the health effects of cobalt. During the period 1982-1992 the surveillance programme showed a profound reduction in the urine level of cobalt (Co-U) from 100-fold to 10-fold above the median level of the unexposed control subjects. In the same period, the airborne cobalt exposure declined from 1356 nmol/m3 to 454 nmol/m3, the Danish occupational exposure limit being 845 nmol/m3. In 1982, when the cobalt exposure was above the occupational exposure limit, the plate painters showed a chronic impaired lung function. The obstructive effects may be similar to some of the effects observed in hard metal workers. In 1988, a study on the effect of cobalt exposure at low levels revealed no inhibitory effects on thyroid function, but the ratio between T4 and T3 increased, indicating that low cobalt exposure may have an impact on the metabolism of thyroid hormones. Parallel studies were conducted on the metabolism and excretion of cobalt. The gastrointestinal uptake of soluble CoCl was considerably higher than the uptake of insoluble cobalt(II) oxide. In addition, it was demonstrated that ingestion of controlled amounts of the soluble cobalt compound resulted in significantly higher concentrations of cobalt in urine and blood (Co-B) from females compared with males (P < 0.01). Future studies will involve epidemiology and genotoxicity to evaluate the previous and present cancer risk, and detailed process-related exposure assessment studies to select the methods most reliable for surveillance of low-dose cobalt exposure.

Cobalt

Determination of 2-naphthylamine in urine by a novel reversed-phase high-performance liquid chromatography method.

A high-performance liquid chromatographic method for the determination of 2-naphthylamine in urine using fluorescence detection was developed. The method validation analysis showed the method to be in analytical control, i.e. the distribution of the difference between the observed and true values of the method evaluation samples did not deviate significantly from the normal distribution. The recovery of the method was 85%. The entire run time of chromatography was 10 min using isocratic elution (acetonitrile-water, 35:65), and the retention time for 2-naphthylamine was 5.8 min. The relative short time of analysis in combination with the low limit of detection (0.272 nmol/l) makes the method potentially applicable for surveillance of occupational and environmental exposure to 2-nitronaphthalene. The developed method is presently used for measurement of 2-naphthylamine in urine samples from workers employed at factories, characterized by a low airborne exposure level of polycyclic aromatic hydrocarbons, i.e. in general less than 25 micrograms/m3. The urine samples of exposed workers (n = 95) showed a 2-naphthylamine range of up to 9.4 nmol/l, whereas unexposed control individuals (n = 114) showed a range of up to 0.87 nmol/l.

2-Naphthylamine

Biomonitoring of genotoxic exposure among stainless steel welders.

A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environmental monitoring of welding fumes and selected metal oxides, biomonitoring of chromium and nickel in serum and urine and mutagenic activity in urine, and evaluation of semen quality were also done. Manual metal arc (MMA) welding and tungsten inert gas (TIG) welding were the dominant welding processes. A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA-AAF)-induced UDS was lower in 23 never-smoking welders than in 19 unexposed never-smokers. Smoking was a confounding factor resulting in significantly higher CA, SCE, NA-AAF binding to DNA and mutagenic activity in urine. Age was also a confounder: CA, SCE, NA-AAF binding to DNA and UDS increased significantly with age. No significant correlation between SCE and CA or between CA and UDS was found. UDS decreased significantly with increasing lymphocyte count and a higher lymphocyte count was seen in MMA welders than in reference persons and in smokers than in non-smokers. Differences in the composition among lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding with MMA is recommended.

Acetoxyacetylaminofluorene

Esophageal speaker articulation of /s,z/: a dynamic palatometric assessment.

Esophageal talker linguapalatal contact patterns and durations during /s/ and /z/ productions were examined using dynamic palatometry instrumentation. It was found that sibilant groove narrowing is a physiologic compensation for a reduced air supply in esophageal speech. The place of esophageal /s, z/ articulation was on the anterior portion of the alveolar ridge as seen in normal speakers. Average medial groove width for esophageal /s/ was narrower than the 5-7-mm groove characteristic of normal speakers. Groove widths averaged 3 mm for /s/ and 4 mm for /z/. Systematic changes in groove widths across speech sounds, syllable position, and vowel context were also observed. Use of a narrower lingual groove was interpreted as a significant articulatory maneuver to meter out a limited intraoral air supply and effect more normal fricative durations.

Articulation Disorders

Comparative study of certified reference materials and quality control materials for the quality assurance of blood-lead determination.

In order to ensure a high standard in the analytical methods used to determine lead in blood, reference materials, quality control materials and several quality assessment schemes exist. However, since 1988 the blood lead level in the European Community has decreased owing to a decline in environmental and occupational exposure; consequently there is a need for certified reference materials (CRMs) at low level. A study of the biological CRMs for blood lead, CRMs 194-196 from the European Community Bureau of Reference (BCR) and the quality control materials STE 901-906 from Nyegaard A/S, and AMI B601-B604 and AMI B701-B705 from the Danish National Institute of Occupational Health (AMI), was made in order to evaluate the control materials AMI B701-B705 against the CRMs 194-196, and to verify the homogeneity and influence of the biological matrix of commercially available blood-lead quality control materials. Internal quality control data were collected and an interlaboratory study was carried out on lyophilized human blood versus lyophilized bovine blood certified for lead. The calculated standard deviations for the BCR CRMs were comparable to the standard deviations for AMI control materials, although the biological matrix was different. No significant difference was demonstrated between the blood-lead levels certified by BCR in 1985 and the levels measured by AMI in 1991, indicating the homogeneity and stability of the lyophilized materials. All analytical results were obtained from selected international laboratories by using atomic absorption spectrometry and anodic stripping voltammetry. The study emphasizes the need for CRMs, control materials and quality assessment schemes for trace elements in biological fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of seafood consumption on the urinary level of total hydride-generating arsenic compounds. Instability of arsenobetaine and arsenocholine.

Arsenobetaine and arsenocholine are considered to be non-toxic and are present as a relatively large proportion of total arsenic in seafoods, and they do not respond to hydride generation. The present study describes the effect of seafood consumption on the urinary concentration of hydride-generating arsenic compounds measured by a newly developed flow injection atomic absorption spectrometric (FI-AAS) method. Consumption of plaice, pighvar and tunny resulted in a 2-fold increase, and consumption of mussels produced a 6-fold increase in the urinary level of hydride-generating arsenic compounds. Hence, a person who has consumed mussels may be suspected of being occupationally or environmentally exposed, if the level of consumption of this seafood is unknown. As the FI-AAS method cannot be used to detect arsenobetaine and arsenocholine, the observed increase in urinary concentration of hydride-generating arsenic compounds after consumption of seafood must originate either from hydride-generating arsenic compounds in the seafood or from degraded arsenobetaine or arsenocholine. The present study has demonstrated that both arsenobetaine and arsenocholine are unstable when incubated in daylight in the presence of hydrogen peroxide, i.e., an oxidizing environment. Hence, it is tempting to speculate that arsenobetaine could be converted into hydride-generating arsenic compounds during storage or cooking of seafood. The feasibility of speciation methods based on high-performance liquid chromatographic (HPLC) separation and on-line analysis by inductively coupled plasma atomic emission spectrometry (ICP-AES) and FI-AAS was also investigated. The FI-AAS system is approximately 35 times more sensitive to the hydride-generating arsenic species than the ICP-AES system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effectiveness of an oral enteric coated vibrio vaccine for use in salmonid fish.

An oral enteric-coated Vibrio anguillarum vaccine was developed by initially coating lyophilized bacteria onto 0.9 mm diameter dextrose sugar beads followed by an Eudragit L-30D coat to serve as enteric protection. Vaccine efficacy was determined by both an in vivo challenge with live pathogen and measurements of serum and mucus antibody levels by ELISA. Survival rates after challenge were 80.3%, 83.3% and 70.3% among the vaccine group, positive and negative controls respectively. Serum and mucus antibody levels were found to be significantly greater in the vaccine group (p less than 0.01). In cases where equivalent survival among tested groups is observed, determination of antibody titer by ELISA may be a preferable indicator of vaccine efficacy.

Animals

Effect of occupational exposure to cobalt blue dyes on the thyroid volume and function of female plate painters.

It has previously been shown that long-term oral exposure to cobalt can cause goiter and myxedema. The effect of industrial cobalt exposure on thyroid volume and function was determined for 61 female plate painters exposed to cobalt blue dyes in two Danish porcelain factories and 48 unexposed referents. Thyroid volume was determined by ultrasonography. The cobalt blue dyes were used in one of two forms, cobalt aluminate (insoluble) and cobalt-zinc silicate (semisoluble). Only the subjects exposed to semisoluble cobalt had a significantly increased urinary cobalt content (1.17 micrograms.mmol-1 versus 0.13 micrograms.mmol-1, P less than 0.0001). These subjects also had increased levels of serum thyroxine (T4) and free thyroxine (FT4I) (P = 0.0001 and 0.0029, respectively), unaltered serum thyroid stimulating hormone (TSH), and marginally reduced 3,5,3'-triiodothyronine (T3), whereas thyroid volume tended to be lower (P = 0.14). The group exposed to insoluble cobalt did not differ significantly in any thyroid-related parameters. No correlation between urinary cobalt and FT4I or thyroid volume was found. The study demonstrates an effect of cobalt on thyroid hormone metabolism.

Air Pollutants, Occupational

[Assessment of the health risk of a residential area contaminated with arsenic and lead. Biological monitoring in Mundelstrup].

Industrial use of toxic substances has resulted in contamination of the outer environment so that polluted area now constitutes a considerable environmental problem. This article describes biological monitoring employed as part of the basis for assessment of the health risk due to contaminated housing soil. As an example was chosen the environmental contamination with lead and arsenic in Mundelstrup Station Town, where a manure factory previously was situated. This area, which was found to be contaminated to a considerable extend with lead and arsenic, was subdivided for living area in 1921. The present material includes 99 residents from a housing area with 30 family houses with gardens in Mundelstrup. At the commencement of the investigation in 1988/1989, blood lead levels and arsenic levels in the urine were measured and the latter were repeated in 1989/1990. For both adults and children, the blood lead levels were the same as in the reference populations. Children below 12 years had in the average higher arsenic contents in the urine compared with women and men: 16.3 mu/l 8.6 mu/l and 11.5 mu/l, respectively. For both children and adults, the arsenic values were similar to those in a limited Danish reference population. In Ruston, an area in USA heavily polluted with arsenic, contamination of the surface was found to correspond to a factor ten times higher than in Mundelstrup where arsenic is measured at a deeper level. Correspondingly, arsenic values in the urine revealed higher average values in children, 30 micrograms/l for females and 65 micrograms/l for males. The average values for the reference group were found to be 11.3-13.0 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Ibuprofen piconol hydrolysis in vitro in plasma, whole blood, and serum using different anticoagulants.

Hydrolysis kinetics of ibuprofen piconol to ibuprofen were determined in vitro in plasma, whole blood, and serum. Varying initial concentrations of ibuprofen piconol with different anticoagulants (EDTA, heparin, citrate, or no anticoagulant) were used in determining the effects each had on the rate of ibuprofen piconol hydrolysis. Varying the initial concentration of ibuprofen piconol did not alter the hydrolysis half-life (concentration range from 50 to 200 micrograms/mL). The anticoagulant used altered the hydrolysis half-life. For plasma, the half-life was shortest when no anticoagulant was present (t 1/2 = 2.5 h) and longer with the presence of anticoagulants; for citrate, t 1/2 = 8.0 h, for heparin; t 1/2 = 15.5 h; and for EDTA, t 1/2 = 161.8 h. Red blood cell uptake of ibuprofen piconol was minimal and ranged from 0.4 to 4.1% over the ibuprofen piconol concentrations used in the study.

Anti-Inflammatory Agents, Non-Steroidal

Correlation of levels of volatile versus carcinogenic particulate polycyclic aromatic hydrocarbons in air samples from smokehouses.

In the present study, data on the concentration of polycyclic aromatic hydrocarbons (PAH) in air samples from fish smokehouses (Nordholm et al. 1986) and meat smokehouses (Hansen et al. submitted for publication) were used to analyze the extent to which six different volatile PAH compounds could function as markers for the total concentration of six different carcinogenic particulate PAH compounds. Although a significant positive correlation was observed between the concentration of each of six volatile compounds and the total concentration of carcinogenic PAH compounds, a particularly good correlation was observed for phenanthrene, anthracene, fluoranthene and pyrene. Calculations of the sensitivity, specificity, positive predictive value and negative predictive value of these potential markers revealed that naphthalene and phenanthrene exhibited the highest sensitivity as markers for total carcinogenic PAH compounds in air samples from smokehouses, whereas fluoranthene and pyrene displayed the highest specificity. However, when the applicability of the six markers was tested on air samples from iron foundries, only naphthalene and pyrene were useful as markers for the carcinogenic compounds. The present study indicates that naphthalene and pyrene might function as markers for carcinogenic PAH compounds, that are present at low concentrations and are therefore difficult and time-consuming to measure directly.

Air Pollutants, Occupational

Occupational and environmental exposure to arsenic--increased urinary arsenic level in children.

The sum of concentrations of inorganic arsenic, methylarsonic acid (MMAA) and dimethylarsinic acid (DMAA) in urine from adults and children living in an unpolluted area was compared with the corresponding sum measured in urine from adults and children living in an area polluted with arsenic and in urine from persons occupationally exposed to arsenic. The median values for 22 adults and 10 children aged 3-10 years living in the unpolluted area were 9.3 and 19.8 nmol As/mmol creatinine, respectively. The corresponding ranges were 3.2-27.9 and 7.7-57.8 nmol As/mmol creatinine, respectively. The difference between adults and children was tested by Mann-Whitney's non-parametric test and found to be significant (p less than 0.0025). No significant difference was found in arsenic concentration in urine from 73 adults and 10 children living in the polluted area compared with the arsenic concentration in urine from those living in the unpolluted area. The arsenic level in urine from adult workers handling arsenic-treated wood was approximately four-fold higher (p less than 0.001), with a maximum recorded concentration corresponding to 814.9 nmol As/mmol creatinine. The arsenic levels in urine from two glass workers were nine- and two-fold higher, respectively. No significantly increased arsenic levels were found in urine from workers impregnating wood and in urine from lead accumulator workers.

Adult

[Exposure of Danish workers to trichloroethylene during the period 1947-1987].

Trichloroethylene, an organic solvent from the group of chlorinated hydrocarbons, has been employed throughout the greater part of this century particularly for degreasing of metals, dry cleaning and as a content in glue and lacquer. Biological monitoring of workers exposed to trichloroethylene as current health supervision has been employed in Danish factories since 1947 as the metabolite trichloroacetic acid in the urine provides an indication of the degree of exposure during the preceding week. In the present investigation, a review was undertaken of all measurements of trichloroacetic acid notified to the Danish Labour Inspection Service during the period 1947-1987 in order to obtain an impression of the historical development in the level of exposure. A total of 2,272 biological measurements distributed among 330 factories, reveal exposure of about the same level from the middle of the fifties to the middle of the seventies but with a distinct fall during the period, as the average value during the first five-year period was 82 mg/l as compared with 18 mg/l at the end of this 40-years period. These data are supplemented by case-histories from the earliest part of the period described by doctors from the Danish Labour Inspection Service.

Air Pollutants, Occupational

Improving alaryngeal speech intelligibility.

Laryngectomized patients using esophageal speech or an electronic artificial larynx have difficulty producing correct voicing contrasts between homorganic consonants. Voicing of a voiceless consonant is the most frequent listener misidentification. A therapy technique is described that emphasizes "pushing harder" on voiceless consonants to improve the intelligibility of alaryngeal speakers. Laryngectomy speech therapy programs should focus first on the production of voiceless consonants before attempting to effect voicing.

Female