Adjustment of creatinine-adjusted values in urine to urinary flow rate: a study of eleven heavy metals and organic substances

The use of urinary monitoring in medical surveillance programs in industry requires development of an accurate and unbiased index of urinary concentrations of occupational toxins. To examine the effects of urinary flow (UF) rate on the standard creatinine (Cn)-adjusted value and the UF- and Cn-adjusted values according to Greenberg and Levine and to Araki et al. for 11 heavy metals and organic substances, 19 metal-foundry workers aged 34–59 years (mean 48), who had been exposed to lead, zinc, and copper for 2–17 (mean 10) years, were studied during four periods of the day under water-free, water-restrictive and water-loading conditions for 6 days. The blood lead concentrations of the 19 workers ranged from 22 to 59 (mean 38) g/dl. The results indicated that there was no significant OF effect on the UF- and Cn-adjusted values of Araki et al. for all urinary substances except mercury and coproporphyrin. On the other hand, the UF- and Cn-adjusted value of Greenberg and Levine was positively correlated with OF rate for all urinary substances, and the standard Cn-adjusted value was either positively or inversely correlated with OF rate for many urinary substances. Therefore, the UF- and Cn-adjusted value of Araki et al. is considered to be applicable to the measurement of most urinary substances under conditions of wide variation in OF rate.     

An analytical method,using GC-MS,for the quantitative determination of urinary thiodiglycolic acid

Summary A GC-MS method is described for the determination of thiodiglycolic acid in 1 ml-samples of urine. The variation coefficient for a series of four determinations was 2.7%. To investigate the variation between values determined on different days, four samples were analysed over periods of 4–8 days. The mean variation coefficient of this series was 6.4 ± 1.3%. From 34 different human urine specimen from males aged between 20 and 55 years, an average level of 0.64 ± 0.32g/ml was determined. From 14 females aged between 19 and 42 years, the corresponding values were 0.51 ± 0.20g/ml.Abbrevations used TdGA Thiodiglycolic acid (also known as dicarboxymethyl sulphide or thiodiacetic acid) - VCM Vinyl chloride monomer     

Enzymatic assay of formic acid and gas chromatography of methanol for urinary biological monitoring of exposure to methanol

Summary An enzymatic assay method for the determination of urinary formic acid is described. Formic acid in urine was cleaved to carbon dioxide and water by formic acid dehydrogenase, whereby NAD⁺ was converted to NADH, which reacted with INT (p-iodonitrotetrazolium violet) in the presence of NAD-diaphorase. The color thus produced was determined at 500 nm. In addition, a simple gas chromatographic method of urinary formic acid is described, in which head space gas of formic acid methylester was applied into the wide bore column. The urinary formic acid concentrations by the enzymatic method agreed well with that by the gas chromatographic method. A simple gas chromatographic method for urinary methanol assay is also described. Acetonitrile was added to an equal volume of urine containing methanol. After centrifugation, the supernatant was injected into gas chromatography (GC). The peaks of urinary methanol and ethanol were separated by GC. Formic acid and methanol in urine of unexposed healthy subjects and workers exposed to methanol were analyzed by the colorimetric and gas chromatographic methods. Geometric mean concentrations of urinary formic acid and methanol in the healthy subjects were 7.82 mg/g creatinine and 1.34 mg/l, respectively. The concentration ratio of formic acid to methanol in the urine of the workers exposed to methanol was calculated to be 3.67 ± 2.10, which agreed with the ratio under a controlled exposure experiment. A slower excretion of formic acid than that of methanol in the urine of a volunteer was also observed.     

Toxicity of and biological monitoring for 1,3-diamino-2, 4, 6-trinitrobenzene and other nitro-amino derivatives of benzene and chlorobenzene

Summary Methaemoglobin-forming capacity of 1,3-diamino-2,4,6-trinitrobenzene (DATNB) was studied in vivo as well as in vitro and compared with those of aniline, phenylenediamine (o- and p-), nitroaniline (o-, m- and p-), nitrobenzene, dinitrobenzene (o-, m- and p-), 1,3,5-trinitrobenzene, chloroaniline (o-, m- and p-), chloronitrobenzene (o-, m- and p-), and 1-chloro-2,4-dinitrobenzene. m-Chloronitrobenzene and two isomers (m- and p-) of dinitrobenzene were the most potent methaemoglobin formers in vivo and it was p-dinitrobenzene when studied in vitro, while the capacity of DATNB was much lower both in vivo and in vitro, being comparable to those of aniline and nitrobenzene. The exposure monitoring by means of the urinalysis for diazo-positive metabolite(s) is applicable to all the compounds studied except DATNB and o-phenylenediamine; conversion of DATNB to the diazo-positive metabolite(s) in urine was very limited, indicating poor metabolism in vivo. Cumulative effects of DATNB was also discussed.This work was supported in part by a research grant from Environment Agency, the Government of Japan     

Chromium bond detection in isolated erythrocytes: a new principle of biological monitoring of exposure to hexavalent chromium

Summary Internal stress to chromium is only relevant in occupational medicine if it is due to the handling of hexavalent chromium. Cr(VI) ions, after uptake by inhalation or percutaneously are carried in the blood plasma and penetrate—depending on the concentration—into the erythrocytes. Due to the intracellular reduction to Cr(III) and the concurrent intracellular protein binding, the erythrocytes represent an easily accessible target organ for quantitative chromium determination after occupational exposure to Cr(VI) compounds. The results of an earlier experimental study indicate that human plasma too is capable of spontaneous reduction of Cr(VI) ions of up to 2 ppm to Cr(III). This plasma reduction capacity (PRC) can be increased and accelerated considerably by adding ascorbic acid (AA). These findings were supported in this investigation by proving a decreased binding of Cr(VI) inside the erythrocytes under the effect of AA. This leads to the assumption that only those Cr(VI) concentrations can penetrate the membrane of the erythrocytes and enter the cell which either come into contact with the membrane during the reduction process or exceed this limit concentration of 2 ppm. Only in these two instances can corresponding chromium findings be analyzed in isolated and washed erythrocytes. These results are compared with those obtained by conventional methods, such as Cr determination in the blood and/or urine. Our findings indicate that a single determination of chromium concentration in the erythrocytes will permit the monitoring of critical cases of Cr(VI) exposure. This is a new type of biological monitoring in the sense of a condensed longitudinal study, in order to find out whether threshold concentrations have been respected over a given period.     

Occupational exposure to polycyclic aromatic hydrocarbons in a graphite-electrode producing plant: biological monitoring of 1-hydroxypyrene and monohydroxylated metabolites of phenanthrene

 Objective. The objective of this study was to assess external and internal exposure to polycyclic aromatic hydrocarbons (PAHs) of workers who are employed in a graphite-electrode producing plant. Additionally we wanted to contribute to the question of biological limit values in order to reduce exposure to tolerable levels. Methods. At five different working places 12 stationary and 16 personal air measurements were carried out to determine the concentrations of phenanthrene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[a]pyrene and dibenz[a, h]anthracene in air. In addition, we investigated the excretion of 1-, 2+9-, 3- and 4-hydroxyphenanthrene and of 1-hydroxypyrene in the urine of 67 workers by a very sensitive and practical high-performance liquid chromatographic (HPLC) method with fluorescence detection; 2- and 9-hydroxyphenanthrene could not be separated with our analytical method. Results. During the production of graphite electrodes significantly higher PAH exposures were found in the baking and impregnation area than in the crushing, graphitisation and conditioning area. The results of personal air measurements (mean values of the sum of eight PAHs) are: 29.3 (baking), 23.4 (impregnation), 5.2 (crushing), 1.3 (graphitisation) and 0.4 μg/m³ (conditioning). Stationary air measurements yielded similar concentrations. Workers employed in the baking and impregnation areas excreted the highest amount of PAH metabolites in urine. The 1-hydroxypyrene concentrations (median) were: 23.4 (baking), 22.0 (impregnation), 9.6 (crushing), 1.8 (graph itisation) and 2.3 μg/g creatinine (conditioning). The corresponding concentrations of the sum of monohydroxylated phenanthrene metabolites (median) were: 23.1, 36.0, 10.4, 4.6 and 7.6 μg/g creatinine. Within the monohydroxylated phenanthrene metabolites 3-hydroxyphenanthrene predominates with a percentage of 43%. Our results showed that a benzo[a]pyrene concentration in air of 2 μg/m³ would lead to 1-hydroxypyrene concentrations in urine of 20–74 μg/g creatinine. That means that corresponding values in the literature which lie between 4.4 and 6.2 μg/g creatinine are due to other conditions of exposure and cannot be applied to graphite-electrode producing plants. Conclusions. Although to date there are no obligatory biological exposure limits for metabolites of PAHs in urine, it must be concluded that the internal PAH exposure is too high at some work places in this plant, as is generally the case in graphite-electrode producing plants. This is probably caused by skin absorption of PAHs. So for the prevention of health hazards by PAH, internal exposure must be measured using biological monitoring. Although it has not been possible to establish biological exposure limits for PAHs until now, we suggest a reduction in skin contact with these substances and thereafter use of the 90th percentile of the results of biological monitoring as “action levels” for corrective measures. Received: 20 May 1996/Accepted: 18 July 1996     

Circadian rhythms in the urinary excretion of heavy metals and organic substances in metal workers in relation to renal excretory mechanism: profile analysis

Summary Circadian rhythms in the urinary excretion of eleven heavy metals and organic substances were examined under free, water-restrictive and water-loading conditions for 6 d (2 d for each of the three conditions) in twenty metal workers exposed to lead, zinc and copper. Circadian rhythms were found for all heavy metals and organic substances as well as for urinary flow (UF) rate, creatinine (Cn) and total urinary solutes (TUS). The Cn rhythm was significantly unparallel to the OF rhythm under the water-loading condition, indicating that the two rhythms were essentially different from each other. Circadian rhythms of the eleven urinary substances were then related to the Cn and OF rhythms, using profile analysis. The results indicated that the rhythms in the manganese, chromium, copper and beta-2-microglobulin excretion depend on the Cn rhythm, i.e. the rhythm of glomerular filtration; the rhythms in the hippuric acid, delta-aminolevulinic acid and TUS excretion are on the OF rhythm, i.e. the rhythm of reabsorption by the distal tubule and collecting duct. On the other hand, the rhythms in the lead, inorganic mercury, cadmium, zinc and coproporphyrin excretion were considered as reflecting complex renal excretory mechanisms.     

Self pregnancy testing in an urban family planning clinic: promising results for a new approach to contraceptive follow-up

BACKGROUND: Immediate initiation of depo-medroxyprogesterone acetate (DMPA) increases continuation and decreases pregnancies compared to conventional (next menstrual period) initiation. A drawback is the need to return in 4 weeks for a repeat pregnancy test to identify any pregnancy that was too early to diagnose on the day of injection. If women can perform home pregnancy tests (HPTs) to detect human chorionic gonadotropin (hCG) in urine, the need for this follow-up visit may be eliminated. This study assesses whether women can perform their own HPT. STUDY DESIGN: This is a single-visit observational trial of an HPT kit. Subjects recruited from a waiting room in an urban family planning clinic received an HPT kit with standard instructions to use immediately. Subjects and a research assistant each interpreted the test. Their results were then compared to a standard cassette type test for detection of hCG performed by clinic staff. kappa was calculated to assess the level of agreement. RESULTS: Three hundred ten subjects enrolled. They were young (mean age, 25.2 years), mostly Hispanic (91%) women. A change in the font and explicitness of the instructions decreased the incidence of invalid tests from 12.7% to 4.8%. The subject and research assistant's interpretation of the test had a high level of agreement, kappa=0.95 [95% confidence interval (CI), 0.92-0.99]. There was also a high level of agreement between the subjects' results and the standard test, kappa=0.88 (95% CI, 0.82-0.95). CONCLUSIONS: Women presenting for pregnancy testing at an urban clinic are able to perform HPTs with a high level of accuracy. The appearance of the instructions influenced the incidence of false-negative and invalid tests. Home pregnancy tests may be useful in follow-up protocols when immediate initiation of DMPA is employed.     

Human biomonitoring pilot study DEMOCOPHES in Germany: Contribution to a harmonized European approach

Human biomonitoring (HBM) is an effective tool to assess human exposure to environmental pollutants, but comparable HBM data in Europe are lacking. In order to expedite harmonization of HBM studies on a European scale, the twin projects COPHES (Consortium to Perform Human Biomonitoring on a European Scale) and DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) were formed, comprising 35 partners from 27 European countries.In COPHES a research scheme and guidelines were developed to exemplarily measure in a pilot study mercury in hair, cadmium, cotinine and several phthalate metabolites in urine of 6–11 year old children and their mothers in an urban and a rural region. Seventeen European countries simultaneously conducted this cross-sectional DEMOCOPHES feasibility study.The German study population was taken in the city of Bochum and in the Higher Sauerland District, comprising 120 mother-child pairs. In the present paper features of the study implementation are presented. German exposure concentrations of the pollutants are reported and compared with European average concentrations from DEMOCOPHES and with those measured in the representative German Environmental Survey (GerES IV).German DEMOCOPHES concentrations for mercury and cotinine were lower than the European average. However, 47% of the children were still exposed to environmental tobacco smoke (ETS) outside their home, which gives further potential for enhancing protection of children from ETS.Compared with samples from the other European countries German participating children had lower concentrations of the phthalate metabolites MEP and of the sum of 3 DEHP-metabolites (MEHP, 5OH-MEHP and 5oxo-MEHP), about the same concentrations of the phthalate metabolites MBzP and MiBP and higher concentrations of the phthalate metabolite MnBP. 2.5% of the German children had concentrations of the sum of 4 DEHP-metabolites and 4.2% had concentrations of MnBP that exceeded health based guidance values, indicating reasons for concern.Continuous HBM is necessary to track changes of pollutant exposure over time. Therefore Germany will continue to cooperate on the harmonisation of European human biomonitoring to support the chemicals regulation with the best possible exposure data to protect Europe’s people against environmental health risks.     

Vaccination coverage rates for Diphtheria,Tetanus, Poliomyelitis and Pertussis booster vaccination in France between 2013 and 2017: Learnings from an analysis of National Health System Real-World Data

BackgroundMaintaining a high vaccination coverage rate (VCR) throughout the lifetime and complying with the National Immunization Program are essential to optimize the protection of the population. The study objectives were to evaluate the evolution of the VCRs and the compliance with the vaccination visits for the diphtheria, tetanus, poliomyelitis and pertussis boosters in France since the changes implemented in the 2013 National Immunization Program.MethodsCumulative booster VCRs were estimated at all vaccination visits, from 2013 to 2017, among persons eligible for a booster vaccination from a 1/97th random sample of French claims data. Broader age groups around the recommended ages by the vaccination schedule (6, 11–13, 25, 45, 65, 75, 85, 95y) were used: all persons aged 5 to 8, 10 to 15, 21 to 29, 41 to 49, 61 to 69, 71 to 79, 81 to 89 and 91 to 99.ResultsOver the study period, the diphtheria-tetanus-poliomyelitis booster VCRs increased, reaching in 2017: 73.3% at 8 years old, 75.6% at 15 years old, 46.6% at 29 years old, 38.4% at 49 years old, 36.3% at 69 years old, 30.8% at 79 years old, 22.1% at 89 years old and 11.0% at 99 years old. The pertussis VCRs were also increasing at all vaccination visits, in particular at the vaccination visits at 6 and 11–13 years old (from 16.4% to 63.8% and from 50.3% to 61.2%, respectively). Delayed vaccinations were observed at all vaccination visits.ConclusionVCRs for Diphtheria, Tetanus, Poliomyelitis and Pertussis booster vaccination increased from 2013 to 2017 while remaining suboptimal across all ages and lower in the adult populations. The analysis also shows that the introduction in 2013 of a pertussis vaccination at 6 years of age was relatively well-established in 2017 while other changes in recommendations were slowly or partially implemented.     

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017.MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)].Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP.Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.