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Biomedical subjects

J M Christensen

Publications and source records attributed to J M Christensen.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

Trace element reference values in tissues from inhabitants of the European Community. V. Review of trace elements in blood, serum and urine and critical evaluation of reference values for the Danish population.

The availability of accurate trace element reference values in human tissues represents an important indicator to the health status of the general population and occupational groups exposed to trace elements. The EURO TERVIHT project (Trace Element Reference Values In Human Tissues) aims to establish and compare trace element reference values in tissues from inhabitants of the European Community as baseline values for clinical/toxicological assessment studies (Sabbioni et al., 1992, Sci. Total Environ., 120: 39-62). In this context, one of the first steps considered is the critical evaluation (state of the art) of existing literature on trace element reference values in blood, serum and urine in the general population of each EC country. This paper reviews the Danish situation.

Adolescent↗
PubMed1994

Correlation between work process-related exposure to polycyclic aromatic hydrocarbons and urinary levels of alpha-naphthol, beta-naphthylamine and 1-hydroxypyrene in iron foundry workers.

In two Danish iron foundries the concentration of polycyclic aromatic hydrocarbons (PAH) in 24 personal air samples of workers employed in selected processes, i.e. melters, melted iron transporters, casters, machine molders, hand molders, shake-out workers and finishing workers, were measured and correlated to levels of 1-hydroxypyrene, alpha-naphthol and beta-naphthylamine in the urine of exposed workers. The highest total airborne PAH concentrations (sum of 15 selected PAH compounds: 9.6-11.2 micrograms/m3) were associated with casting, machine molding, and shake-out. The highest concentrations of the sum of six selected airborne carcinogenic PAH compounds were found for melting, casting and machine and hand molding. As seen in other working environments involving low-level PAH exposure, the content of naphthalene was high, in general exceeding 85% of the total content of PAH compounds. The present study demonstrates that 1-hydroxypyrene is a useful and direct biomarker of low-dose occupational exposure to PAH compounds. Molding and casting had the highest pyrene levels in iron foundries. Furthermore, the data shows that levels of beta-naphthylamine in urine are significantly elevated in iron foundry workers. Hand molders, finishing workers and truck drivers tended to have the highest levels. Concerning alpha-naphthol the highest concentrations were measured in urine from casters and shake-out workers. With regard to epidemiologic studies demonstrating that molders and casters have a higher risk of lung cancer, the present study suggests that the elevated risk may be due to exposure to carcinogenic PAH compounds in iron foundries, particularly in some high-risk work processes, e.g. casting and molding. In addition, the present study suggests that biological monitoring of 1-hydroxypyrene and beta-naphthylamine may be used to estimate the individual exposure, which seems to be correlated with exposure during individual work processes.

2-Naphthylamine↗
PubMed1994

Determination of the urinary metabolites of styrene: estimation of the method evaluation function and evaluation of reference values in Danish subjects.

A European study on styrene exposure was initiated in 1989 to evaluate the health effects of environmental and occupational exposure. A part of this study included the development of an analytical method for use in a biological monitoring program. The urinary metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA) were quantitated by a direct and convenient high-performance liquid chromatography method. Urine samples were diluted with eluent and analysed by HPLC with a C8 reversed-phase column and a buffer to acetonitrile (9:1) eluent with a counterion added. The detector used was a variable UV detector and the wavelength was lambda = 210 nm. The method was statistically evaluated by a method evaluation demonstrating no systematic error. The uncertainty was 23.8 mumol/l and 11.5 mumol/l for MA and PGA, respectively. The limit of detection (LOD) of MA is 71.4 mumol/l and the LOD of PGA is 34.5 mumol/l, sufficiently low for the measurement of styrene exposure at a low exposure level. The present study indicates that reference values for MA and PGA are low. The fraction of reference values below LOD was 0.80 for MA and 0.66 for PGA; consequently, the reference values were described by a non-parametric one-sided tolerance interval. The 95% one-sided upper tolerance limits calculated for MA and PGA were 31.0 mumol/mmol creatinine and 20.1 mumol/mmol creatinine, respectively, with the coverage 0.95 +/- 0.045 for both metabolites. The method has been used for biological monitoring in several studies of environmentally and occupationally exposed subjects in concentrations up to 200 mumol/mmol creatinine for MA and 150 mumol/mmol creatinine for PGA.

Air Pollutants, Occupational↗
PubMed1993

Determination of chromium in blood and serum: evaluation of quality control procedures and estimation of reference values in Danish subjects.

This paper describes analytical methods to estimate environmental and occupational exposure levels of chromium in blood and serum by Zeeman atomic absorption spectrometry. Also reported is an internal quality control procedure involving a combination of an online quality control and subsequent statistical evaluation of the quality control results to evaluate the performance of the analytical methods. The solubilization of the blood by the proteinase Subtilisin A resulted in a recovery of chromium of 106 +/- 4.5%; the uncertainty was approximately 10% at a chromium level of 1 microgram l-1. The detection limit (LOD) for chromium in serum was 0.17 micrograms l-1 and 0.20 micrograms l-1 for chromium in blood. The LODs were sufficiently low for the determination of chromium in a large fraction of reference populations not occupationally exposed. The present study indicates that reference values for chromium in blood and serum are low but within the range in recent investigations, i.e. 0.04-0.35 micrograms l-1 in serum and 0.12-0.34 micrograms l-1 in human whole blood. The fraction of reference values below LOD was between 0.45 and 0.57 for chromium in serum and blood. Consequently, the reference populations were described by distribution free one-sided tolerance intervals and the precision of the estimation of the tolerance intervals was expressed as coverage intervals. The 95% one-sided tolerance limit calculated for chromium in serum was 0.60 micrograms l-1 with the coverage interval (95 +/- 4.8) percent at a probability of 0.95. Thus, the probability was 0.975 that the tolerance interval covers at least 90.2% of the distribution. In addition, the probability was 0.025 that the tolerance interval covers more than 99.8% of the population. It was only possible to calculate the 90% tolerance interval for chromium in blood with the coverage interval at 0.90 probability. The one-sided tolerance interval for chromium in blood was 0.37 micrograms l-1 with the coverage interval (90 +/- 9.9) percent at a probability of 0.90.

Chromium↗
PubMed1993

A short-term cross-over study on oral administration of soluble and insoluble cobalt compounds: sex differences in biological levels.

This paper describes a blind cross-over study on the gastrointestinal uptake of soluble and insoluble cobalt compounds (8.5 mumol/day) in 12 male and 11 female volunteers. In a controlled study it was found that the gastrointestinal uptake of the soluble cobalt compound cobalt chloride was considerably higher than the uptake of the insoluble cobalt compound cobalt oxide (urine ranges: < 0.17-4373 and < 0.17-14.6 nmol/mmol creatinine, respectively). Surprisingly, it was shown that ingestion of controlled amounts of soluble cobalt compound resulted in significantly higher urinary cobalt levels (P < 0.01) in females (median: 109.7 nmol/mmol creatinine) than in males (median: 38.4 nmol/mmol creatinine). The results suggest that the gastrointestinal uptake of cobalt is higher for females than males. The present study shows that the normal levels of cobalt in blood and urine in a non-random-selected group of Danes are low. As the fraction of values below the detection limit of the analytical method was 0.19 and 0.33 for urinary cobalt in females and males, respectively, distribution-free one-sided tolerance intervals were chosen to describe the values. The precision of the estimate of the tolerance intervals was expressed as coverage intervals. In females the 95% one-sided tolerance limit calculated for cobalt in blood and urine was 8.48 and 55.10 nmol/l with coverage intervals of 90% +/- 6.5% and 95% +/- 4.2% at a probability of 0.95, respectively. Even though the studied groups of males and females were not representative for the general population, the study indicates that oral exposure may be important in occupational settings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Danish external quality assessment scheme: an interlaboratory comparison study on lead, cadmium and chromium in lyophilized human blood concentrate.

A Danish External Quality Assessment Scheme (EQAS) was carried out by the Danish National Institute of Occupational Health during the period 1988-1992. The scheme was implemented for 29 international laboratories from 15 countries assaying lead, cadmium, and chromium in human blood to ascertain the systematic error and uncertainty of the analytical methods. In the survey the quality control material AMI B701-B705, based on lyophilized human whole-blood concentrate, were used. As an estimate of the true values the reference values used in this evaluation were (a) the computed values, i.e., sum of the basal and spiked trace element concentration, and (b) the consensus values normally used in the Danish EQAS. This international evaluation of lead, cadmium, and chromium in human blood demonstrated that the use of lyophilized human blood concentrate quality control materials combined with this scheme is valuable in estimating the systematic error and the uncertainty of the analytical methods. For evaluating analytical performance, the computed values were preferable to the consensus values for lead and cadmium in human blood. Due to analytical difficulties suitable reference values were not established for chromium in blood. The study revealed analytical difficulties for cadmium and chromium in human blood. The assessment of laboratories according to established performance indexes indicates that few laboratories can maintain these performance indexes.

Cadmium↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗