Erik Holst

Sunlight-induced DNA damage in human mononuclear cells

In this study of 301 blood samples from 21 subjects, we found markedly higher levels of DNA damage (nonpyrimidine dimer types) in the summer than in the winter detected by single‐cell gel electro‐phoresis. The level of DNA damage was influenced by the average daily influx of sunlight < 50 days prior to blood sampling. The 3 and 6 day periods before sampling influenced DNA damage the most. The importance of sunlight was further emphasized by a positive association of the DNA damage level to the amount of time the subjects had spent in the sun over a 3 day period prior to the sampling. The effect of sunlight was comparable to the interindividual variation, indicating that sunlight exposure and the individuals background were the two most important determinants for the basal level of DNA damage. Influence of other lifestyle factors such as exercise, intake of foods, infections, and age could not be detected. Our results suggest that sunlight penetrates the outer layer of the human epidermis and damages the DNA in mononuclear cells circulating in the vessels of the skin.—Møller, P., Wallin, H., Holst, E., Knudsen, L. E. Sunlight‐induced DNA damage in human mononuclear cells. FASEB J. 16, 45–53 (2002)

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.

Man-made mineral fibre size distributions utilizing unbiased and fibre length biased counting methods and the bivariate log-normal distribution

Abstract The bivariate log-normal distribution and the marginal and conditional distributions are introduced for the description of diameter ( D ) and length ( L ) distributions of airborne man-made mineral fibres (MMMF). Measured fibre sizes fit this distribution well. The accumulated length-diameter distribution has several unique properties regarding characterization of bulk MMMF and dispersed dust as well as of aerodynamic and biological properties of airborne MMMF. This distribution is shown to be the distribution function of a stochastic variable D L defined as the diameter of a fibre drawn from a fibre population with a probability proportional to the fibre length. The distribution of D L is easy to measure and some underlying formulae can be taken directly from stereology. If ( D,L ) is bivariate log-normally distributed, then D L is log-normal. The variances of In D L and In D are identical and a simple formula relates the parameters of the distribution of In D L to the parameters of the bivariate log-normal distribution.

Iron, manganese, copper and titanium in welding fume dust on filters for internal and external quality assurance

SummaryFilters charged with welding fume dust were developed and produced for internal and external quality assurance to evaluate and improve the performance of analytical methods used for monitoring iron, manganese, copper and titanium in the working environment. The filters were simultaneously loaded, using a Sputnic air sampling unit containing 100 cellulose nitrate filters. The welding fume dust was collected in industrial working conditions where Metal Inert Gas welding in construction steel was being carried out. The metal concentrations on the filters were close to the metal concentrations from environmental and industrial exposure. The homogeneity of the filter materials was evaluated to document the suitability of the air sampler in producing quality control materials. The filters were homogeneous within 5.0–12.7% according to amount of metal. The welding fume dust loaded on the filters was (0.2021±0.0093 mg/filter) and the amounts of metals loaded on the filters were (34.6±6.4 μg/filter, 16.0±0.8 μg/filter, 2.4±0.1 μg/filter) for iron, manganese and titanium, respectively. Normalizing the amount of metal according to the welding fume dust improved the homogeneity. The most satisfactory results were obtained for manganese and titanium, for which within batch variation was below 6.3%. The Sputnic air sampler was shown to be suitable in preparing quality control materials, although a few improvements are needed for future experiments, such as the method of charging the dust and rules for outlier exclusion.

Lyophilized human whole blood for internal and external quality assurance of lead in blood assays.

SummaryLyophilized human whole blood control material containing lead was prepared for internal and external quality assurance to evaluate and improve the analytical performance of lead.The samples were prepared in four different concentrations from outdated human whole blood stabilized with glucose and a citrate/phosphate buffer and provided under clean room conditions to avoid contamination. The lyophilized samples are easy to reconstitute with water. The materials were evaluated according to a statistical model.The lead concentrations in the specimens are close to blood lead levels usually following environmental and industrial exposure, particular in occupational health to the control of lead exposure at work regulations. The materials are available to the commercial as well as the scientific community.The Danish External Quality Assessment Scheme (DEQAS) for lead in blood is intended to complement the internal quality control for the Danish laboratories assaying lead in blood. During 1990 the scheme will be tested in an international external assessment scheme.

Evaluation of blood lead levels in Danes for the period 1976–1987

SummaryBlood lead was measured in 504 men and 548 women in 1976 living in the Glostrup area, Denmark. The subjects were first seen in 1976 at age 40, and in 1981, 5 years later as 45 years old. 451 men and 410 women were reexamined. Finally 151 men, at age 51 were included in this study. The median blood lead levels averaged 130 and 90 μg/ l in 1976 and 90 and 60 μg/l in 1981 in male and female, respectively. In 1987 the median blood lead level of the male subjects was 71 μg/l.By use of quality control samples, long term storage control and statistical methods a decrease in the median blood lead level of 45% was estimated for the male subjects for the period 1976–1987, probably due to a parallel decline in atmospheric lead pollution and decrease of occupational lead exposure.

Danish External Quality Assessment Scheme: An interlaboratory comparison study on lead, cadmium and chromium in lyophilized human blood concentrate

SummaryA 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 materials 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.

Fibre size characterization and size analysis using general and bivariate log-normal distributions

Abstract Fibre sizes have to be described by both diameter d and length l . There is a stochastic relationship between D and L which may be given by the bivariate distribution function for the bivariate stochastic variable ( D , L ). A measure w = ad r l s is introduced and formulae are developed for the distribution function, the expected value and the variance for the random variable W = aD r L s . The expression for w was chosen because such important characteristics as fibre surface area (approximately), volume, aspect ratio and settling speed are covered. Corresponding expressions are given for ( D w , L w ), i.e. the diameter and the length of fibres sampled randomly from a fibre population with a probability proportional to the w -value of the individual fibres. By combination the random variable X w = kD w p L w q , is described. When ( D , L ) is assumed to be bivariate log-normally distributed the derived distributions will also be log-normal, respectively, bivariate log-normal and expressions are given for the parameters of these distributions in terms of the parameters of the distribution of ( D , L ), i.e. the mean value and the variance of the marginal distribution of ln D , respectively, In L and the correlation between ln D and ln L .

Variability of total mass and other measures of small samples of particles

Abstract Aerosol measurement frequently requires that an aerosol sample be withdrawn from its environment. The sampled mass is not strictly proportional to the sampled volume because mass is present in discrete entities. This introduces a fundamental variability in the estimated particle mass concentration, particularly important for small particle samples. The total amound of any particle measure, ω, including mass, of the sampled particles is described by its coefficient of variation, CV. The results also apply for sampling a volume of liquid in which particles are dispersed, and can under some conditions be used for, e.g. analysis of weight per cent of asbestos in bulk powder, and microscopical analysis of total particle mass or projected area in a specimen. The fundamental coefficient of variation CV is also given for the special case of individual particle diameters having a log-normal distribution. Exact knowledge of the size distribution at the upper tail is critical in determining CV, as illustrated by calculating CV for a range of right truncated log-normal distributions. A mass variability equivalent diameter, MVED, is defined, by which the mass variability of a polydisperse aerosol can be described in terms of number variability (Poisson) of a monodisperse aerosol with diameter MVED. A population of airborne particles, sized by microscopy is used to show that in order to obtain CV N > 6500, while only 100 particles would be needed if the measure was particle number. The variability is termed fundamental because it is the lowest achievable variability for given sample size and size distribution. This must be recognized, when determining overall uncertainty budgets for analytical procedures, including use of direct reading particle mass monitors for which a simple equation is given for calculating CV.

A statistical test for the mean squared error

The likelihood ratio test for a specified value of the mean squared error is derived assuming observation from a normal distribution. The mean squared error is a well established tool for assessing closeness to a target value when bias as well as sampling error (or measurement error) is taken into account. While the distributional properties of the mean squared error are well known, so far no simple tests for hypotheses concerning the MSE have been established. An explicit expression for the likelihood ratio test statistic is provided together with a simple intuitive interpretation. The distribution of the test statistic under the null-hypothesis is discussed and it is shown that the specified value of the MSE enters as a scale-parameter. This means that it is only necessary to determine the distribution of the test-statistic when the hypothesized MSE equals one. In principle, the null distribution of the test-statistic depends on the partition of the MSE into the bias component and the variance. However,...