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Abstract: Objective: Exposure to polychlorinated biphenyls (PCBs) is considered to have culminated between 1950 and 1970 in Japan, and exposure through diet, the major exposure route, has decreased significantly over the last 10 years. The primary goal of the present study was to investigate the long-term trends and congener profiles of serum and dietary levels of PCBs using historical samples. Methods: Using banked samples collected in 1980, 1995, and 2003 surveys, we determined the daily intakes and serum concentrations of 13 PCB congeners (#74, #99, #118, #138, #146, #153, #156, #163, #164, #170, #180, #182, and #187) in women. Results: The total daily PCB intake [ng/day, geometric mean (geometric standard deviation)] decreased significantly from 523 (2.5) in 1980 to 63 (3.2) in 2003. The serum total PCB level (ng/g lipid) in women <40 years of age decreased significantly from 185 (1.8) in 1980 to 68 (1.8) in 2003. In contrast, the level in women >50 years of age increased significantly from 125 (1.7) in 1980 to 242 (1.7) in 2003. Specifically, the serum concentrations of hexa (#138, #146, #153, #156, #163, and #164) and hepta (#170, #180, #182, and #187) congeners increased significantly. A comparison of the serum PCB levels of women born from 1940 to 1953 revealed that their serum total PCB level was significantly higher in the 2003 survey [242 (1.7), n = 9] than in the 1995 [128 (2.0), n = 17] surveys. This increase in the total PCB level was attributable to increases in the hepta congener groups. Conclusion: Present results suggest a decreased rate of elimination of hepta congeners with aging in females, rather than a birth-generation phenomenon.

Intestinal barrier function declines with aging. We evaluated the effect of dietary fibers and indigestible oligosaccharides on intestinal barrier function by altering the microbiota of the elderly. The feces were anaerobically cultured with indigestible dextrin, inulin, partially hydrolyzed guar gum (PHGG), lactulose, raffinose, or alginate, and the fermented supernatant was added to inflammation-induced Caco-2/HT29-MTX-E12 co-cultured cells. Our data showed that inulin- and PHGG-derived supernatants exerted a protective effect on the intestinal barrier. The protective effect was significantly positively correlated with total short-chain fatty acids (SCFAs) and butyric acid production in the supernatant and negatively correlated with the claudin-2 (CLDN2) gene expression in the cultured cells. Furthermore, we showed that the CLDN2levels are regulated by butyric acid. Thus, inulin and PHGG can change the intestinal environment of the elderly and maintain the intestinal barrier by accelerating the production of SCFAs and modifying the expression levels of barrier function-related genes.

ABSTRACTBackground:Lactoferrin (bLF) is an iron-binding multifunctional protein that is abundant in milk. In mice, it inhibits catechol-O-methyltransferase (COMT) activity and increases blood levodopa levels. However, the clinical effects are unknown.Objective:The objective of this study was to determine the effect of bLF on the kinetics of levodopa in blood.Design:The effects of the concomitant administration of a combined formulation of levodopa and an aromatic amino acid decarboxylase inhibitor and bLF on the concentration of levodopa in blood and its metabolism were assessed in eight healthy subjects. In addition, we analyzed the association with clinical factors and evaluated whether clinical factors affected the COMT inhibitory activity of bLF in vitro.Results:Although not statistically significant, the peak plasma concentration (Cmax) of levodopa increased by 18.5%. From the results of the stratified analysis of total cholesterol, a relationship with ΔCmaxwas predicted. Therefore, bLF was reacted with cholesterol in the presence of lecithin and sodium deoxycholate in vitroto evaluate COMT inhibitory activity, and an increase in inhibitory activity was observed. By contrast, the ester compound cholesteryl oleate had no effect. The inhibitory activity of free fatty acids, which are known to interact with bLF, was also enhanced.Conclusion:The COMT inhibitory activity of bLF is not effective in elevating blood levodopa levels. However, in humans with high lipid levels, such as cholesterol, interactions may enhance the inhibitory effect, resulting in the enhanced absorption of levodopa.Trial registration: ID, UMIN000026787, registered 30 March 2017; URL, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030749Trial registration:UMIN Japan identifier: UMIN000026787

Examples of cases in clinical medicine as well as occupational and environmental health studies are described to indicate the conditions under which reliable results for exposure assessment were obtained through biological monitoring. Biological monitoring is a solution-oriented practical approach. Four check points are described for effective biological monitoring, i. e., identification of the type of biological specimens available, selection of correct sampling time, a sensitive and selective analytical method, and interpretation based on a full knowledge of the metabolism., (Key Words: biological monitoring: clinical toxicology; environmental health: occupational health.) INTRODUCTION The concept of biological monitoring expanded rapidly in the 1950s. Professor R.T. Williams' book Detoxication Mechanists (1) still offers [...]

Many investors wonder why Japanese firms have had considerably higher price/earnings ratios than U.S. firms. Some have claimed that the cross-shareholdings among Japanese firms bias P/Es upward. This is not always the case, however. The adjustment formula used by practitioners requires careful consideration. (Reprinted by permission of the publisher.)

Abstract Objectives To determine whether any vital signs can be used to quickly identify brain lesions in patients with impaired consciousness. Design Cross sectional observational study. Setting Emergency department of [...]

To simplify the procedures to estimate biological occupational exposure limits (BOELs) by use of the ratio of geometric mean (GM) concentration of un‐metabolized organic solvent in urine (U‐GM) over GM organic solvent concentration in air (A‐GM) (the [U‐GM/A‐GM] ratio). Occupational Exposure Limits (OELs) and BOELs were cited from publications from the Japan Society of Occupational Health (JSOH) and the American Conference of Governmental Industrial Hygienists (ACGIH). Data on [U‐GM/A‐GM] and the SLOPE of exposure‐excretion regression line were collected from published articles (men and women were treated separately). Correlation analysis and paired ttest were employed as the method to examine statistical significances. Significant linear correlation was established between the SLOPE and the [U‐GM/A‐GM]. Thus, it was considered to be possible to calculate the SLOPE value from the [U‐GM/A‐GM]. Previously established equation of BOEL = SLOPE × OEL allowed to estimate BOEL values in 22 cases of data sets. The comparison of the estimated BOELs with the existing BOELs (JSOH's BOELs and ACGIH's BEIs) in terms of the ratio of [(estimated BOEL)/(existing BOEL)] showed that the ratios for the 22 cases probably distributed log‐normally with a GM of 0.85, and the maximum was 5. Therefore, the estimated BOEL may be generally applicable in occupational health when BOEL remains yet to be established. In the worst case, the estimated BOEL may be five times greater than it should be. The recommended procedures for application of estimated BOEL values were described. Simplified procedures for estimation of BOEL values are proposed.

To test the reliability of the procedures (described in a previous article) for estimation of biological occupational exposure limits (BOELs). Data on four organic solvents (styrene, ethyl benzene, isopropyl alcohol and tetrachloroethylene) were obtained from recent publications and added to previously cited data for 10 organic solvents. Regression analysis was used for statistical evaluation. The previously reported results obtained using 10 solvents were reproduced by the analysis with 14 solvents. Repeated randomized division of the 14 sets into two subgroups of equal size followed by statistical comparisons did not show a significant difference between two regression lines. This reproducibility suggests that the procedures used to estimate BOELs may be applicable across many solvents, and this may be of particular benefit for protecting the health of workers who work with skin‐penetrating solvents.

Background: New drug and medical device introduction in Japan usually lags behind that in the West. Many reports indicate that in Japan, the associated risks are considered greater than the benefits recognized in other countries. This study aimed to compare the relationship between risk-benefit perception and acceptance of medical technologies in 3 leading markets.Methods: A tripartite cross-sectional survey of the general public was used. In total, 3345 adults in the United Kingdom, the United States, and Japan participated, and sexes and age groups were equally represented. Questions about the perception of risk, benefit, and acceptance of medical and other scientific technologies, and trust of medical product providers or regulatory authorities were included.Results: Five-step Likert coding for risk/benefit/acceptance of 4 medical items (x-rays, antibiotics, vaccines, and cardiac pacemakers) and 6 general items (such as automobiles and airplanes) were collected. Relationships between benefit perception and acceptance were linear for 4 medical technologies. The relationship had a similar slope but was shifted downward in Japan compared with the UK and US (P< .01), suggesting a lower acceptance in Japan for all benefit perceptions. The trend was the same between risk perception and acceptance, except for slopes that were negative. Correspondence analysis showed a strong correlation among acceptance of medical technologies, benefits of medical technologies, trust in doctors, and trust in the Department of Health. The UK and US attributes were clustered with positive responses such as “useful,” “acceptable,” and “trustworthy,” whereas Japan was clustered with intermediate to negative responses such as “neither” and “untrustworthy.”Conclusions: Acceptance of medical technologies was low in Japan because of significant differences in trust for doctors and authorities compared with that in the UK and US. This is a possible basis for delays of 24 to 60 months for medical product approval in Japan.

The Capitanian stage is characterized by marine anoxia possibly related to the extinction, although the global redox structure of the Capitanian ocean has not been constrained. We newly report a nitrogen isotope (δ15N) record from a paleo‐atoll limestone at the top of a mid‐Panthalassan seamount to constrain the spatial extent and duration of the Capitanian marine anoxia. The δ15N value of limestone after acid treatment is substantially high for ∼5‐Myr up to +28‰, the highest through the Phanerozoic oceans, suggesting that the nitrogen source (nitrate) was substantially enriched in 15N via denitrification within subsurface oxygen‐deficient zones (ODZs; O2< 5 µM). Numerical modeling of nitrogen isotope dynamics in the upwelling system along the seamount suggests that the possible minimum δ15N value of a global deep‐oceanic nitrate reservoir was ca. +9‰ in the Capitanian (∼4‰ higher than at the present). Furthermore, a redox‐dependent nitrogen isotope mass balance model constrained the global redox structure of the Capitanian superocean. Substantially reducing conditions (O2≤ 20 µM) prevailed at intermediate water depths (100–1,000 m), in association with expanded ODZs with anoxic/euxinic cores along continental margins (≥ ∼0.4% of global ocean volume), while the deep‐ocean remained to be more oxidizing (O2≤ 60 µM). The enhanced open‐ocean productivity associated with the low sea‐level and high nutrient flux to the ocean resulted in the global ocean deoxygenation during the cooling stage. Our model is consistent with previous geologic observations and with a possible link between the long‐term (∼5‐Myr) development of marine dysoxia and the extinction. The Capitanian stage is a peculiar stage characterized by several environmental changes including marine anoxia, possibly related to the large extinction. Previous studies reported the evidence for marine anoxia developed at least locally in the Capitanian, although the spatial extent and duration of anoxia in the superocean Panthalassa in the stage have been poorly constrained. Bioavailable nitrogen is essential for life and the nitrogen isotopic composition of sedimentary record is useful to reconstruct the global nitrogen cycle in association with oceanic redox condition in the past. We report a ∼5‐Myr‐long nitrogen isotope record from a shallow‐water limestone in the lost mid‐superocean during the Capitanian. This unique record reveals major changes in global nitrogen cycle in the stage, that is, the appearance of a substantially 15N‐enriched oceanic nitrate reservoir indicating enhanced anaerobic respiration under reducing conditions. Numerical modeling further constrains that the reducing water masses (O2< 20 μM) prevailed at intermediate water depths (100–1,000 m) in the superocean, in association with the expanded oxygen‐deficient zones with anoxic/euxinic cores developed along the continental margins (at least twice as much as in the modern oceans). Our new model is consistent with the scenario that the long‐term subsurface anoxia/euxinia contributed to the shelf extinction. N isotope record from the mid‐Panthalassa suggesting expanded oxygen‐deficient zones in mid‐water depths (>∼0.4% of global ocean volume)Substantially reducing ocean in association with the low sea‐level, high nutrient flux to the ocean, and enhanced open‐ocean productivityA possible link between the long‐term (∼5‐Myr) deep‐water anoxia/euxinia along the continental margins and the shelf extinction N isotope record from the mid‐Panthalassa suggesting expanded oxygen‐deficient zones in mid‐water depths (>∼0.4% of global ocean volume) Substantially reducing ocean in association with the low sea‐level, high nutrient flux to the ocean, and enhanced open‐ocean productivity A possible link between the long‐term (∼5‐Myr) deep‐water anoxia/euxinia along the continental margins and the shelf extinction

Estimation of biological occupational exposure limit values for selected organic solvents from logartihm of octarol water partition coefficient: Toshio Kawai, et al. Osaka Occupational Health Service Center, Japan Industrial Safety and Health Association For several organic solvents (solvents in short), biological occupational exposure limits (BOELs) have been established for unmetabolized solvents in urine, based on the solvent exposure‐urinary excretion relationship. This study was initiated to investigate the possibiliy of estimating a BOEL from the Pow(the partition coefficient between n‐octyl alcohol and water), a physico‐chemical parameter. Data were available in the literatures for exposure‐excretion relationship with regard to 10 solvents for men and 7 solvents for women. Statistical analysis revealed that the slopes (after correction for molecular weights and logarithmic conversion) of the exposure‐excretion regression lines linearly correlated (p<0.01) with the log Powvalues the respective solvents. No significant difference (p>0.05) was observed between men and women, and it was acceptable to combine the data for the two sexes. Thus the log Pow‐log slope relation was represented by a single equation for both sexes. Based on the observations, procedures were established to estimate BOEL values from Pow. Successful estimations of BOELs for styrene, tetrahydrofuran and m‐xylene (a representative of xylene isomers) were calculated as examples. The present study proposed promising procedures for estimation of a BOEL from the Pow.

Comparison of the exposure‐excretion relationship between men and women exposed to organic solvents: Toshio Kawai, et al. Osaka Occupational Health Service Center The present study was initiated to examine if application of the same biological occupational exposure limits (BOELs) for organic solvents is applicable across the sexes. A survey was conducted in 69 microscale enterprises in a furniture‐producing industrial park. In practice, 211 men and 52 women participated in the survey. They worked in a series of production process, and were exposed to solvent vapor mixtures. The exposure intensities were monitored with two types of diffusive samplers, one with carbon cloth (for solvents in general) and the other with water (for methyl alcohol) as adsorbents. Solvents in the adsorbents and headspace air from urine samples were analyzed with capillary FID‐GC. The measured values were subjected to linear regression analysis followed by statistical evaluation for possible sex‐related differences in slopes. Essentially no significant difference was detected between men and women in regression line parameters including slopes. Possible differences in the cases of acetone and toluene were discussed and excluded. With the exceptions for acetone and toluene, the present study did not detect any clear differences between men and women. In examinations of past reports, no support for the observed differences was found. The present findings deserve further study so that a solid conclusion can be formed.

The mechanisms that generate robust ionic oscillation in circadian pacemaker neurons are under investigation. Here, we demonstrate critical functions of the mitochondrial cation antiporter leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1), which exchanges K+/H+in Drosophilaand Ca2+/H+in mammals, in circadian pacemaker neurons. Letm1knockdown in Drosophilapacemaker neurons reduced circadian cytosolic H+rhythms and prolonged nuclear PERIOD/TIMELESS expression rhythms and locomotor activity rhythms. In rat pacemaker neurons in the hypothalamic suprachiasmatic nucleus (SCN), circadian rhythms in cytosolic Ca2+and Bmal1transcription were dampened by Letm1knockdown. Mitochondrial Ca2+uptake peaks late during the day were also observed in rat SCN neurons following photolytic elevation of cytosolic Ca2+. Since cation transport by LETM1 is coupled to mitochondrial energy synthesis, we propose that LETM1 integrates metabolic, ionic, and molecular clock rhythms in the central clock system in both invertebrates and vertebrates.

Solvent Use in Private Research Laboratories in Japan: Comparison with the Use in Public Research Laboratories and on Production Floors in Industries: Takaaki HANADA, et al. Kyoto Industrial Health Association— Solvents used in production facility‐affiliated private laboratories have been seldomly reported. This study was initiated to specify solvent use characteristics in private laboratories in comparison with the use in public research laboratories and on production floors. Elucidation of the applicability of conclusions from a public laboratory survey to private institutions is not only of scientific interest but also of practical importance. A survey on use of 47 legally stipulated organic solvents was conducted. The results were compiled for April 2011 to March 2013. Through sorting, data were available for 479 unit workplaces in private laboratories. Similar sorting for April 2012 to March 2013 was conducted for public research laboratories (e.g., national universities) and production floors (in private enterprises) to obtain 621 and 937 cases, respectively. Sampling of workroom air followed by capillary gaschromatographic analyses for solvents was conducted in accordance with regulatory requirements. More than one solvent was usually detected in the air of private laboratories. With regard to solvent types, acetone, methyl alcohol, chloroform and hexane were prevalently used in private laboratories, and this was similar to the case of public laboratories. Prevalent use of ethyl acetate was unique to private laboratories. Toluene use was less common both in private and public laboratories. The prevalence of administrative control class 1 (i.e., an adequately controlled environment) was higher in laboratories (both private and public) than production floors. Solvent use patterns are similar in private and public laboratories, except that the use of mixtures of solvents is substantially more popular in private laboratories than in public laboratories.

Astronomical theory predicts that ~2 Myr eccentricity cycle have changed its periodicity and amplitude through time because of the chaotic behavior of solar planets, especially Earth-Mars secular resonance. Although the ~2 Myr eccentricity cycle has been occasionally recognized in geological records, their frequency transitions have never been reported. To explore the frequency evolution of ~2 Myr eccentricity cycle, we used the bedded chert sequence in Inuyama, Japan, of which rhythms were proven to be of astronomical origin, covering the ~30 Myr long spanning from the Triassic to Jurassic. The frequency modulation of ~2 Myr cycle between ~1.6 and ~1.8 Myr periodicity detected from wavelet analysis of chert bed thickness variation are the first geologic record of chaotic transition of Earth-Mars secular resonance. The frequency modulation of ~2 Myr cycle will provide new constraints for the orbital models. Additionally, ~8 Myr cycle detected as chert bed thickness variation and its amplitude modulation of ~2 Myr cycle may be related to the amplitude modulation of ~2 Myr eccentricity cycle through non-linear process(es) of Earth system dynamics, suggesting possible impact of the chaotic behavior of Solar planets on climate change.

Objectives: To examine the amount of daily dietary Cd intake (Cd-D) as the most influential non-occupational source of exposure to Cd for women among general populations in Korea. Design: Foci were placed on: 1. time trends in the amount of dietary Cd intake as the estimated values and instrumental analysis values; 2. the current trends in Cd-D and two biological exposure markers of Cd in blood (Cd-B) and in urine (Cd-U); 3. the Cd-D by food groups and their time trends. Method and Materials: Cd-D by instrumental analysis and Cd in blood (Cd-B) and urine (Cd-U) were cited from previous representative Korean reports. In addition, Cd-D was estimated from data on food intakes (by food groups) published in the Korea National Health and Nutrition Examination Survey and the Cd contents by each food group reported in previous representative publications. Results and Discussion: The estimated Cd-D for Korean women in 2007 was 14.82 μg per day, of which 9.74 μg per day was from plant foods and 5.09 μg per day was from animal foods. The Cd-D of plant origin accounted for 65.7%, indicating that Cd-D for Korean women is mostly from plant foods. Among the plant food groups, ‘potatoes and starch’ and ‘grains and cereals (including rice)’ were not only the major energy source in Korea but the largest Cd-D accounts among the food groups, followed by ‘seaweed’ as the third source. ‘Fish and shellfish’ were the largest Cd-D source among the food groups of animal origin. As for time trends, the estimated Cd-D decreased by 13% over a 10 year period, whereas no clear reduction was observed in Cd-B and Cd-U. Conclusion: The main Cd-D source for Korean women is foods of plant origin. ‘Grains and cereals’, and ‘potatoes and starch’, are the most influential sources of exposure to Cd. Overview of Cd-D exposure over 10 years showed a trend of a slight decrease, but there was no noteworthy reduction in Cd-B and Cd-U.

Stability in Urine of Authentic Phenylglyoxylic and Mandelic Acids as Urinary Markers of Occupational Exposure to Styrene: Yoko Eitaki, et al. Osaka Occupational Health Service Center, Japan Industrial Safety and Health Association—Phenylglyoxylic acid (PhGA) and mandelic acid (MA) are two popular urinary markers of occupational exposure to styrene, but PhGA has been considered to be relatively unstable when urine samples are stored. This study was initiated to examine the stability of PhGA in urine under two storage conditions, i.e., at room temperature (at 25°C) and in refrigeration (at 4°C) for up to 14 days. The experiments showed that no substantial decrease was observed in either PhGA or MA even at room temperature within one day, but, depending on urine samples, a gradual decrease in PhGA took place both at 4°C and more markedly at 25°C when kept for a week. Further reduction was observed in two weeks even at 4°C. No reduction was observed in MA up to two weeks both at 4°C and at 25°C. The observation on stability of MA and limited stability of PhGA (i.e., no significant decrease for 4 days when stored as refrigerated) was confirmed by a repeated experiment. Further analyses disclosed that PhGA when stored at 4°C tended to be more unstable when urine samples were alkaline (e.g., at pH 8) rather than acidic (e.g., at pH 6 or below), but the trend varied subject to individual samples. Thus, the practical recommendation is that urine samples should be analyzed on the day of collection if all possible, or kept at 4°C, or more preferably at –20°C. Refrigeration will allow storage of up to 4 days without substantial decrease in either PhGA or MA.

Abstract

Secular Trends and Geographical Variations in the Dietary Intake of Polybrominated Diphenyl Ethers (PBDEs) Using Archived Samples from the Early 1980s and Mid 1990s in Japan: Yasuhiko Wada, et al.Hyogo College of Medicine—A retrospective exposure assessment among the general population for polybrominated diphenyl ethers (PBDEs) was conducted using dietary surveys. We analyzed samples of food duplicate portions collected in the early 1980s (1980 survey: N=40) and the mid 1990s (1995 survey: N=39) from female subjects (5 participants from each of 8 sites per survey except for one site) living throughout Japan, from the north (Hokkaido) to the south (Okinawa). The study populations in the 1980 and 1995 surveys were different, but lived in the same communities. We measured four PBDE congeners [2,2’,4,4’-tetrabrominated diphenyl ether (tetraBDE): #47; 2,2’,4,4’,5-pentaBDE: #99; 2,2’,4,4’,6-pentaBDE: #100; and 2,2’,4,4’,5,5’-hexaBDE: #153] in the diet. #99 was the most abundant congener in the diet (49% of the total PBDEs), followed by #47 (33%), #100 (12%) and #153 (6%). Regional variations found in the 1980 survey decreased in the 1995 survey. The total daily intake of PBDEs (ng/d) [GM (GSD)] in the 1980 survey [91.4 (4.1)] was not significantly different from that in the 1995 survey [93.8 (3.4)] for the total population, nor did it differ among the sites including Shimane, in which a 20-fold increase in serum concentrations was observed in the same population1). In consideration of the significant increases in the serum concentration, inhalation may be more important than food ingestion as the route of human exposure to PBDEs.

Abundant evidences demonstrate that deuterium oxide (D2O) modulates various secretory activities, but specific mechanisms remain unclear. Using AtT20 cells, we examined effects of D2O on physiological processes underlying β-endorphin release. Immunofluorescent confocal microscopy demonstrated that 90% D2O buffer increased the amount of actin filament in cell somas and decreased it in cell processes, whereas β-tubulin was not affected. Ca2+ imaging demonstrated that high-K+-induced Ca2+ influx was not affected during D2O treatment, but was completely inhibited upon D2O washout. The H2O/D2O replacement in internal solutions of patch electrodes reduced Ca2+ currents evoked by depolarizing voltage steps, whereas additional extracellular H2O/D2O replacement recovered the currents, suggesting that D2O gradient across plasma membrane is critical for Ca2+ channel kinetics. Radioimmunoassay of high-K+-induced β-endorphin release demonstrated an increase during D2O treatment and a decrease upon D2O washout. These results demonstrate that the H2O-to-D2O-induced increase in β-endorphin release corresponded with the redistribution of actin, and the D2O-to-H2O-induced decrease in β-endorphin release corresponded with the inhibition of voltage-sensitive Ca2+ channels. The computer modeling suggests that the differences in the zero-point vibrational energy between protonated and deuterated amino acids produce an asymmetric distribution of these amino acids upon D2O washout and this causes the dysfunction of Ca2+ channels.

The purposes of the present study are (1) to develop a sensitive analytical method to measure 1-bromopropane (1-BP) in urine, (2) to examine if 1-BP or bromide ion (Br) in urine is a useful biomarker of exposure to 1-BP, and (3) to identify the lowest 1-BP exposure concentration the method thus established can biomonitor. A factory survey was carried out on Friday, and 33 workers (all men) in cleaning and painting workshops participated; each worker was equipped with a diffusive sampler (carbon cloth KF-1500 as an adsorbent) to monitor 1-BP vapour for an 8-h shift, and offered a urine sample at the end of the shift for measurement of 1-BP and Br in urine. In addition, 10 non-exposed men offered urine samples as controls. The performance of the carbon cloth diffusive sampler was examined to confirm that the sampler is suitable for monitoring time-weighted average 1-BP vapour exposure. A head-space GC technique was employed for analysis of 1-BP in urine, whereas Br in urine was analysed by ECD-GC after derivatization to methyl bromide. The workers were exposed to vapours of seven other solvents (i.e. toluene, xylenes, ethylbenzene, acetone, etc.) in addition to 1-BP vapour; the 1-BP vapour concentration was 1.4 ppm as GM and 28 ppm as the maximum. Multiple regression analysis however showed that 1-BP was the only variable that influenced urinary 1-BP significantly. There was a close correlation between 1-BP in urine and 1-BP in air; the correlation coefficient (r) was 0.9 with a narrow variation range, and the regression line passed very close to the origin so that 2 ppm 1-BP exposure can be readily biomonitored. The correlation of Br in urine with 1-BP in air was also significant, but the r (about 0.7) was smaller than that for 1-BP, and the background Br level was also substantial (about 8 mg l-1). Thus, it was concluded that 1-BP in end-of-shift urine is a reliable biomarker of occupational exposure to 1-BP vapour, and that Br in urine is less reliable.

The objective of this study was to establish a hand-saving method to measure phenylmercapturic acid (PMA) and to examine urinary PMA as a marker of occupational exposure to benzene at levels less than 1 ppm. A simple HPLC method was developed to analyse PMA by monitoring absorption at 195 nm of the efzeni uent from an ODS-3 column with acetonitrile-methanol-perchloric acid-water as a mobile phase. The detection limit of the method was 0.2 μg l-1 with sufficient reproducibility. The method was applied to end-of-shift urine samples from 70 gasoline station attendants exposed to up to 107 ppb benzene, and 20 non-exposed controls of both sexes. Time-weighted average (TWA) exposure to benzene was measured by diffusive sampling. A regression analysis was applied to examine the quantitative relationship between the intensity of exposure to benzene and PMA in the end-of-shift urine samples. Multiple regression analysis showed no effects of age, sex, smoking and co-exposure to toluene and xylenes on urinary PMA. There was a linear relationship between TWA benzene exposure and urinary PMA (r = 0.60-0.67, P < 0.01). Background PMA in urine of the non-exposed controls was low and scattering of PMA around the regression line was narrow so that those with 20 ppb benzene exposure can be separated from the non-exposed by urinalysis for PMA. Thus, urinary PMA is sensitive enough for biological exposure monitoring of those exposed to less than 1 ppm benzene.

Abstract: To assess the levels of daily dietary intake of selenium (Se) among the general Chinese population, a series of field surveys were conducted in the 1990s. Samples of 24-h duplicates of foods were collected from 500 participants (300 in 6 cites and 200 from 4 villages). Se levels were determined by microwave digestion followed by inductively coupled plasma-mass spectrometry (ICP-MS), and the measurements were compared with FCT (Food Composition Tables)-based estimates. The average daily intake of Se was 69.2 µg/d (79.9 and 53.1 µg/d in urban and rural areas, respectively) by instrumental determination and 35.1 µg/d (36.7 and 32.7 µg/d) by FCT-based estimation. As the distribution of Se should be uneven within China, the FCT-based estimation is of a limited value and the ICP-MS determination of Se is more accurate and reliable when evaluating the nutritional status of local people. Taking ICP-MS-based values, Se intakes were lower in rural areas than in urban areas, and the intakes of about half of the people in rural areas were less than the Recommended Daily Allowance (RDA) in China of 50 µg/d. The low intake might be resulted from difference in the types of food consumed. Thus, the dietary intake of Se basically meets the recommended RDA in most of urban areas, but insufficiency may be still a nutritional and public health problem in some rural areas.

Apoptosis is involved in both the cellular and humoral immune system destroying tumors. An apoptosis-inducing factor from HL-60 myeloid leukemia cells was obtained, purified, and sequenced. The protein found has been identified as a human complement factor B-derived fragment Bb, although it is known that factor B is able to induce apoptosis in several leukemia cell lines. Monoclonal antibodies against fragment Ba and Bb inhibited the apoptotic activity of factor B. When the purified fragment Bb was used for apoptosis induction, only the anti-Bb antibody inhibited Bb-induced apoptosis, and not the anti-Ba antibody. The apoptosis-inducing activity was found to be enhanced under conditions facilitating the formation of Bb. Blocking TNF/TNFR or FasL/Fas interactions did not interfere with the factor B-induced apoptosis. CD11c (iC3bR) acts as the main subunit of a heterodimer binding to fragment Bb in the apoptosis pathway, and the factor B-derived fragment Bb was found to possess the previously unknown function of inducing apoptosis in leukemic cells through a suicide mechanism of myeloid lineage cells during the differentiation stage. J. Cell. Physiol. 185:280–292, 2000. © 2000 Wiley-Liss, Inc.

Despite increasing public concern of the possible health effects of lead (Pb) on general populations, reports on Pb levels in blood (Pb-B) and urine (Pb-B), as well as Pb intake via foods (Pb-F) for many Asian countries are scarce. The present study was initiated to elucidate the extent of non-occupational Pb exposure among general populations in East and Southeast Asia. In 1991–1997, peripheral blood, morning spot urine and 24-hour food duplicate samples were collected from 20 to 50 non-smoking adult women in each of four cities in Southeast Asia and five cities in Mainland China, and two cities each in Japan and Korea. The samples were wet-ashed and then analyzed by inductively coupled plasma mass spectrometry for Pb-B, Pb-U and Pb-F. Measures after logarithmic conversion were subjected to ANOVA and regression analysis. Geometric mean values in cities in East and Southeast Asia were in ranges of 32–65 μg/L for Pb-B, 2.1–7.5 μg/g cr for Pb-Ucr, and 7–32 μg/day for Pb-F. The values for a combination of two cities of Tokyo and Kyoto, Japan (38 μg/L for Pb-B and 9.3 μg/day for Pb-F) appeared to be lower than the values for other Asian cities, and the values for all Japan (thus including both urban and rural areas) were even lower (19 μg/L for Pb-B and 7.7 μg/day for Pb-F). Comparison of Pb uptake via respiratory and dietary routes showed that Pb via dietary route accounted for 15% of the total in Manila where Pb in air was high (ca. 650 ng/m³), whereas it was 54% in Tokyo+Kyoto where Pb in air was low (ca. 75 ng/m³). When compared internationally, Pb-F and Pb-B in Asia in general are similar to or somewhat higher than the levels in Europe and USA, whereas the levels in Japan are probably lower than the two latter areas. In Asia, Pb-F accounted for 15–54% of all Pb sources, the percentage being variable depending on local conditions especially Pb in atmospheric air. Am. J. Ind. Med. 38:271–280, 2000. © 2000 Wiley-Liss, Inc.

Cholinergic regulation of the suprachiasmatic nucleus (SCN) has been extensively studied although the intracellular signaling mechanisms are not well understood. We examined immunostaining for phospholipase C-β (PLC-β) families that couple to muscarinic acetylcholine receptors (mAChR) and demonstrated the expression of PLC-β1 and β4 in the mouse SCN. Ca2imaging analysis indicated that the M1-mAChR antagonist, pirenzepine blocked carbachol-induced Ca2elevation in the SCN and the response was equivalent between the wild type and the PLC-β4-knockout mice. In addition, the knockout mice displayed locomotor and temperature rhythms coupling to 24 h light/dark cycles. Therefore, it was proposed that PLC-β1 but not PLC-β4 was involved in the mAChR-mediated Ca2signaling in the SCN.

Promising biological monitoring for occupational 1,2‐dichloropropane exposure by urinalysis for unmetabolized solvent: Toshio Kawai, et al. Osaka Occupational Health Service Center The aim of this study was to examine the applicability of urinalysis for unmetabolized solvent to biomonitor 1,2‐dichloropropane (1,2‐DCP) exposure. Thirty three male printers exposed to 1,2‐DCP and 5 nonexposed male controls participated in the study. The 8‐hr average levels of exposure to 1,2‐DCP in air and 1,2‐DCP in the end‐of‐shift urine samples were measured with capillary FID‐GC. The geometric mean (the maximum) concentrations was 7.1 ppm (23.1 ppm) for 1,2‐DCP in air, and the level in urine (without correction for urine density) was 77 μg/l(247 μg/l). A regression analysis showed a correlation coefficient of 0.909 (p<0.01). No 1,2‐DCP was detected in the urine samples from nonexposed subjects. The high correlation and low background (essentially zero) showed that urinalysis for unmetabolized 1,2‐DCP is a promising tool for biomonitoring of occupational exposure to this carcinogenic solvent at lower levels (e.g. <1 ppm).

The Effects of a Health Promotion Program on Body Mass Index: Katsuya Furuki, et al. Department of Occupational Health, Kyoto Industrial Health Association—The objectives of the study were to clarify the effects of a health promotion program approved by the “Total Health Promotion Plan (THP)” sponsored by the Japanese Ministry of Labour on body mass index (BMI) and to identify the potential value of BMI. A group of 392 men and 115 women aged 26‐55 years who had taken part in THP for four years were the subjects of this follow‐up study. Longitudinal change in BMI and other medical parameters (including systolic and diastolic blood pressure, total cholesterol and HDL‐cholesterol) were analyzed in the THP group in comparison with those of a control group (matched by sex, age and term of follow‐up). No significant difference in medical parameters was detected between the THP group and the control group, but major findings indicate that change in BMI is closely related to change in other medical parameters and that lifestyle deterioration of overweight workers increases BMI and lifestyle improvement (especially dietary habits) reduces BMI. The present study suggests that lifestyle improvement results in a decrease in BMI followed by improvement in medical parameters. Both BMI and change in BMI appear to be comprehensive indicators of the health status of overweight workers.

Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that antibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor- receptor)-dependent processes. We purified a previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as β2-microglobulin (β2m), which has been previously known as thymotaxin and is a part of the HLA class I antigen complex. β2m acts on both T-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed that biotinilated β2m recognized an epitope distinct from those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that β2m plays a previously unrecognized and important role in regulating the elimination of tumor cells, which occurs as a result of the action of β2m as an apoptosis-inducing factor.

The present study was initiated in order to identify the best marker of occupational exposure to cyclohexanone among cyclohexanone and its metabolites in urine. To examine if diffusive samplers are applicable to personal monitoring of exposure to cyclohexanone in workroom air, the performance of carbon cloth to adsorb cyclohexanone in air was studied by experimental exposure of the cloth to cyclohexanone at 5, 10, 25 or 50 ppm (i.e. 20, 40, 100 or 200 mg m-3) for up to 8 h. Cyclohexanone in the exposed cloth was extracted with carbon disulphide followed by gas chromatographic (GC) analysis. The cloth adsorbed cyclohexanone in proportion to the concentration (up to 50 ppm) and the duration (up to 8 h), and responded quantitatively to a 15 min exposure at 100 ppm. In a field survey, end-of-shift urine samples were collected from 24 factory workers occupationally exposed to cyclohexanone (up to 9 ppm) in combination with toluene and other solvents. Urine samples were also collected from 10 subjects with no occupational exposure to solvents. The urine samples were treated with acid or an enzyme preparation for hydrolysis, and extracted with dichloromethane or ethyl acetate. The extracts were analysed by GC for cyclohexanone, cyclohexanol, and trans- and cis-isomers of 1,2- and 1,4-cyclohexanediol. Both cyclohexanol and trans-1,2-cyclohexanediol in urine correlated significantly with time-weighted average intensity of exposure to cyclohexanone. Although trans -1,4-isomer was also excreted, its quantitative relation with cyclohexanone exposure could not be established, because the solvent extraction rate was low and unstable. Excretion of cis-isomers was not confirmed. The two analytes, cyclohexanol and trans-1,2-cyclohexanediol, appeared to be equally valid as exposure markers, but the latter may be superior to the former in the sense that it is sensitive enough to separate the exposed from the non-exposed at 1 ppm or less cyclohexanone exposure.

Personal monitoring of 8‐hour time‐weighted average intensity of exposure with diffuse samplers and analysis of shift‐end urine for total trichloro‐compounds (TTC) and other metabolites were conducted in two groups of workers in China, one (121 subjects) exposed to tetrachloroethylene (TETRA) alone, and the other (38 subjects) exposed to a mixture of TETRA and trichloroethylene (TRI). Urinalysis was also performed on samples from 103 non‐exposed controls. A linear exposure‐excretion relationship could be observed in both groups of workers. Comparison of these results with those of Japanese TETRA‐workers suggested the presence of ethnic difference in TETRA metabolism. Urinary metabolite levels were markedly lower in the mixed (TETRA + TRI) exposure group as compared to previous findings in a group exposed to TRI alone. The observation indicates that metabolism of TRI is suppressed by the co‐exposure to TETRA in humans.

To identify the method of choice for analysis of urine for 2,5-hexanedione (2,5-HD) as an indicator of occupational exposure to n-hexane, the end-of-shift urine samples of 36 n-hexane exposed male workers and 30 non-exposed male workers were analyzed for 2,5-HD under three conditions of hydrolysis, i.e. enzymic hydrolysis at pH 4.8, acid hydrolysis at pH 0.5, and without hydrolysis. The 2,5-HD concentrations thus determined were examined for correlation with 8-h, time-weighted average exposure concentrations of n-hexane measured by diffusive sampling. The regression analysis showed that the 2,5-HD concentrations without any hydrolysis correlated best with the intensity of exposure to n-hexane. No 2,5-HD was detected in the urine of the non-exposed subjects under the analytical conditions with no hydrolysis. Thus, the analysis without hydrolysis was considered to be the method of choice from the viewpoint of simplicity in analytical procedures, sensitive separation of the exposed from the non-exposed, and quantitative increase in the amount of 2,5-HD after n-hexane exposure.

The relationship of the intensity of occupational vapor exposure to isopropyl alcohol (IPA) with urinary excretion of acetone and unmetabolized IPA was studied in 99 printers of both sexes, who were exposed to up to 66 ppm IPA (as time-weighted average), together with toluene, xylenes, methyl ethyl ketone and/or ethyl acetate. Acetone and IPA concentrations in urine were studied also in 34 non-exposed subjects. Acetone was detectable in the urine of most of the non-exposed, and the urinary acetone concentration increased in proportion to the IPA exposure intensity (r = 0.84 for observed, non-corrected values), whereas the correction for creatinine concentration or specific gravity of urine did not give a larger correlation coefficient. IPA itself was not found in the urine of the non-exposed, and was detectable in urine of only those who were exposed to IPA above a certain level, e.g. 5 ppm. The present study results suggest that urinary acetone is a valuable index for biological monitoring of occupational exposure to IPA as low as 70 ppm.

The exposure intensity during a shift and the metabolite levels in the shift-end urine were examined in male workers exposed to either benzene (65 subjects; the benzene group), toluene (35 subjects; the toluene group), or a mixture of both (55 subjects; the mixture group). In addition, 35 non-exposed male workers (the control group) were similarly examined for urinary metabolites to define background levels. A linear relationship was established between the intensity of solvent exposure and the corresponding urinary metabolite levels (i.e. phenol, catechol and quinol from benzene, and hippuric acid and o-cresol from toluene) in each case when one of the three exposed groups was combined with the control group for calculation. Comparison of regression lines in combination with regression analysis disclosed that urinary levels of phenol and quinol (but not catechol) were lower in the mixture group than in the benzene group when the intensities of exposure to benzene were comparable, indicating that the biotransformation of benzene to phenolic compounds (excluding catechol) in man is suppressed by co-exposure to toluene. Conversely, metabolism of toluene to hippuric acid was suppressed by benzene co-exposure. Conversion of toluene to o-cresol was also reduced by benzene, but to a lesser extent. The significance of the present findings on the mutual suppression of metabolism between benzene and toluene is discussed in relation to solvent toxicology and biological monitoring of exposure to the solvents.

A survey on styrene exposure was conducted in five small to medium-sized fiber-reinforced plastic (FRP) boat plants utilizing carbon felt dosimeters as personal and stationary samplers to measure 4 h (TWA) exposure during workday afternoons. The heaviest exposure, up to 256 ppm by personal sampling and 174 ppm by stationary sampling, took place during the lamination on a mold to produce a boat shell, and the work inside narrow holds also resulted in exposures of a comparable degree. Styrene levels were much lower in other auxiliary works. The TWA of exposure in an entire boat production was estimated to be 40–50 ppm. Installation of several flexible hoses as an exhaust system was proved to be effective in decreasing the vapor concentration. Gas masks were also useful in reducing the exposure. Urine samples were collected from 96 male workers at the end of 8h work (4 h in the morning and 4 h in the afternoon) and also from 22 nonexposed male subjects, and analyzed for mandelic acid (MA), phenylglyoxylic acid (PhGA), and hippuric acid (HA). When the results of urinalyses were compared with 4-h styrene TWA as monitored by personal sampling, the best correlation was obtained with MA + PhGA/creatinine (the correlation coefficient, 0.88), followed by MA (0.84). For these two cases, regression lines and 95% confidence limits for the group means and for the individual values were calculated. The urinary levels of MA, PhGA, and HA in the 22 nonexposed male subjects were also tabulated.

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.

Physical examination was carried out on 13 workers exposed to vapours of catechol and phenol. The intensity of exposure was such that the average concentrations of catechol and phenol were 1.8 ppb and 55.6 ppb, respectively, with an occasional peak up to 70 ppb and 260 ppb, respectively. Chief complaints of the workers were related to upper respiratory tract, such was confirmed by CMI Health Questionnaire as well as by clinical examination. Possible disturbance of catecholamine metabolism, haematopoiesis, or hepatic and renal functions was ruled out. Biological half-life of catechol, calculated from the result of the factory survey and rat experiments, was comparable to that of phenol. No evidence was obtained to suggest metabolic inhibition between phenol and catechol. Colorimetric method for determination of catechol in air and in urine in the presence of phenol is described.

Affirmative results were obtained to prove that diffusion-absorption on carbon-desorption dosimetry is applicable to monitor exposure to mixed vapors of organic solvents (n-hexane: ethyl acetate : toluene=1:4:1). While most of seven carbon felt preparations tested failed to absorb n-hexane in humid air or the amounts absorbed were no longer proportional to vapor concentrations even in dry air when the sum of the three vapor concentrations were over 3 times workroom threshold limits, two preparations revealed capacity to absorb n-hexane even in the air with relative humidity of 95%. Furthermore, the amounts absorbed during four hour exposures were linearly related to the vapor concentrations of at least 4.5 times workroom threshold limits when the three vapor concentrations were summed up, and, at lower concentrations, the absorbed amounts were proportional to the exposure duration of up to eight hours. Short term peak exposure could also be detected; the ratio between the observed and the expected was about 80% at lowest.

Since 1980, the Japan Federation of Occupational Health Organizations has been conducting an external quality control survey for biological monitoring under a contract with the Ministry of Labour of the Japanese Government. The number of participating organizations has increased from 91 in 1980 to 179 in 1987. The items in the program were lead and free erythrocyte protoporphyrin concentrations in blood, and lead, coproporphyrin, S-aminolevulinic acid, chromium, hippuric acid, methylhippuric acid, total trichloro-compounds, mandelic adic, and phenol concentrations in urine. Evaluation was based on a scoring system. The scores were on the slope of major axis for probable ellipse, the slope of regression line, square root of error mean square for regression, performance indices, and the difference between ‘true’ and observed values of each sample. There was a gradual improvement in the evaluation scores as a function of time. The improvement was paralleled by the adoption of modern analytical methods such as flameless atomic absorption spectrometry for blood-lead measurement and high-performance liquid chromatography for urinary hippuric acid determination in many participants. These methods are simple in operation and reliable in performance. It was considered very probable that the program promoted the adoption.

The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels.

Summary Blood and urine samples were collected from 57 male Japanese solvent workers [exposed to n-hexane (Hex-A), ethyl acetate, and toluene (Tol-A) at 1.5, 2.3, and 2.3 ppm as GM-TWA, respectively] and also from 20 male nonexposed workers at the end of a 8-h shift, and analyzed for n-hexane (Hex-B) and toluene (Tol-B) in blood, and n-hexane (Hex-U), toluene (Tol-U), 2,5-hexanedione [both with (HD-U/cHYD) and without hydrolysis (HD-U/sHYD)] and hippuric acid (HA-U) in urine. Regression analysis showed that both Hex-B and Tol-B correlated significantly with corresponding exposure to the solvents. Solvents in urine (Hex-U and Tol-U) also correlated with solvents in air but with smaller correlation coefficients than the solvents in blood. Both HD-U/cHYD and HD-U/sHYD showed significant correlation with Hex-A, but HA-U failed to do so with Tol-A. Based on the correlation among biological exposure indicators and solvent concentration in air, sensitivity as an exposure indicator was compared between the solvent in blood and the metabolite in urine in terms of the lowest solvent concentration at which the exposed can be separated (with statistical significance) from the nonexposed (the lowest separation concentration; LSC). The LSC was 3.9 ppm for Hex-B, 1 to 2 ppm for HD-U/sHYD and 10 to 30 ppm for HD-U/cHYD, suggesting that HD-U/sHYD is superior even to Hex-B in detecting low n-hexane exposure; this high sensitivity of HD-U/sHYD is due to the absence of HD-U/sHYD in the urine from the nonexposed. In contrast, Tol-B (with LSC of 2.4 ppm) was more sensitive than HA-U; no LSC for HA-U could be obtained because of lack of correlation with Tol-A at low toluene exposure.

Summary A preparation containing m-dinitrobenzene, in which the solvent was a mixture of ethylene glycol and diethylene glycol and ammonium sebacate was added as a co-existing solute, did not produce methemoglobinemia both in humans and in guinea pigs when applied percutaneously. Skin application experiments were carried out with guinea pigs in order to analyze the mechanism of this negative observation. When the concentration of diethylene glycol was 15% (W/W) or less and that of ethylene glycol was 77.5% (W/W) or more, the solution produced methemoglobinemia in guinea pigs. Replacement of ammonium sebacate with diammonium salt of adipic acid or malonic acid without any modification of the solvent also made the formulation capable of methemoglobin-formation in guinea pigs. All of the formulations and their modifications, regardless of their positive or negative capacity to produce methemoglobinemia, did not provoke skin irritation in guinea pigs.

Summary Possible color vision loss was examined with Lanthony's new color test and Ishihara's color vision test in 261 solvent workers and 120 controls (48 men and 72 women). The solvent workers were exposed to either predominantly toluene [46 ppm as geometric mean (GM); 63 men and 111 women], tetrachloroethylene alone (13 ppm; 30 men and 34 women), or a mixture (14 men and 9 women) of tetrachloroethylene (12 ppm) and trichloroethylene (7 ppm). The only instances of color vision loss that were detected in either the exposed workers or the controls were six cases of red-green loss (all in men). These six cases of red-green loss showed an unbiased distribution between the exposed workers and the nonexposed controls.

The relationship between the 8-h time-weighted average (TWA) intensity of exposure toN, N-dimethylformamide (DMF) vapor (with little possibility of skin contact with liquid DMF) and the subsequent excretion ofN-monomethylformamide (MMF) precursor in shift-end urine samples was examined in 116 workers exposed to DMF and 92 workers exposed to DMF in combination with toluene. Urinary MMF level was examined also in 42 non-exposed subjects. The TWA vapor concentration in breathing zone air of each worker was successfully measured by means of a recently developed diffusive sampler in which water was used as an absorbent. The examination of gas chromatographic (GC) conditions for MMF determination showed that the formation of MMF was not saturated when the injection port temperature was set at 200°C, reached a plateau at 250°C, and showed no additional increase at 300°C. There was a linear relationship between DMF in air and MMF in urine with a regression equation ofy =1.65x + 1.69 (r = 0.723,P<0.01), wherey is MMF (unit; mg/l, uncorrected for urine density) in urine andx is DMF (ppm) in air, when only those exposed to DMF were selected, and the injection port temperature was set at 250°C. From this equation, it was possible to estimate that about 10% of the DMF absorbed will be excreted into urine as the MMF precursor. The slope of the regression line was significantly smaller among those exposed to DMF and toluene in combination as compared with those with DMF exposure only.

Summary Exposure of 34 male workers to combined toluene, styrene and methanol was monitored by personal diffusive sampling of solvent vapours in breathing zone air, analysis of shift-end blood for the 3 solvents and analysis of shift-end urine for hippuric, mandelic and phenylglyoxylic acids and methanol. The exposure of most of the workers was below current occupational exposure limits. Regression analysis showed that a linear correlation exists for each of the 3 solvents between any pairs of the concentrations in air, blood and urine. Namely, toluene, styrene and methanol concentrations in blood obtained at the end of a shift are linearly related to the time-weighted average intensity of exposure to corresponding solvents, and also hippuric, mandelic and phenylglyoxylic acids as well as methanol in shift-end urine. The concentrations of hippuric, mandelic and phenylglyoxylic acids as well as methanol in urine correlated with the respiratory exposure intensity. Comparison of the present results with the exposure — excretion relationship after occupational exposure to the individual solvent showed that no modification in metabolism is induced by the combined exposure when exposure is low, as in the present case.

Summary The exposure-excretion relationship and possible health effects of exposure to methanol vapor were studied in 33 exposed workers during the second half of 2 working weeks. Urinary methanol concentrations were also determined in 91 nonexposed subjects. The geometric mean value for methanol in urine samples from the latter was < 2 mg/1 (95% upper limit of normal, < 5 mg/l) when log-normal distribution was assumed. Among the exposed workers, the methanol level in urine samples collected prior to the work shift exceeded the 95% upper limit of normal. The time-weighted average intensity of exposure to methanol vapor was measured using personal sampling devices (in which water severed as an absorbent) in 48 cases of methanol exposure (i.e., 2 of the 33 exposed workers failed to provide urine samples, whereas 17 subjects were examined twice). Methanol concentrations in urine were determined in samples collected at the end of the shift from the 48 exposed cases as well as from 30 nonexposed controls. There was a significant correlation between the exposure to methanol vapor at concentrations of up to 5,500 ppm and the levels of methanol measured in the shift-end urine samples. The calculation indicated that a mean level of 42 mg methanol/l urine (95% confidence range, 26–60 mg/kg) was excreted in the shift-end urine sample following 8 h exposure to methanol at 200 ppm (the current occupational exposure limit). Dimmed vision and nasal irritation were among the most frequent symptoms complained during work. Three cases showing clinical signs of borderline significance were identified.