Toxicological aspects of cadmium and occupational health activities to prevent workplace exposure in Japan: A narrative review.

Chemicals are an essential part of modern manufacture processes. Their use must be managed with great attention in occupational settings to avoid serious detrimental effects to the health of employees. For example, cadmium compounds are indispensable for the production of nickel-cadmium rechargeable batteries or as chemical stabilizer in plastics. It is an exceptionally toxic heavy metal and personnel exposed to cadmium in the workplace meet with potential health risks that can lead to the development of kidney, skeletal and respiratory disorders. In consequence, proactive and systematical development of occupational hygiene and health activities are necessary to reduce chemical exposure to cadmium in the workplace. This review describes the known facts of cadmium toxicity, the biological effects of cadmium exposure, possible regulation measures to prevent occupational cadmium exposure in three industrial health management systems and discusses future cooperation programs in these systems, proactive safety activities and occupational safety and health management strategies.

Effects of sodium monofluoroacetate on glucose, amino-acid, and fatty-acid metabolism and risk assessment of glucose supplementation.

Sodium monofluoroacetate (SMFA; also known as compound 1080) is a highly toxic chemical; therefore, accidental exposure and intentional misuse are of great concern. SMFA intoxication is reportedly caused by the inhibition of aconitase. However, the pathogenesis underlying SMFA intoxication is not clear. This study was conducted to elucidate the acute effects of SMFA on glucose, amino-acid, and fatty-acid metabolism and to assess glucose supplementation as a possible alleviator or aggravator in SMFA intoxication. Rats were assigned to three groups: SMFA+saline, SMFA+glucose, and control (i.e., no SMFA), and blood samples were analyzed at 3 hours after SMFA or saline (control) administration. Additional rats were used for the monitoring of blood-glucose and lactate concentrations for 10 hour- and 14-day survival rates. SMFA increased the serum-citrate, serum-pyruvate, and blood-lactate concentrations. However, despite significant increases in these parameters when SMFA was administered with glucose, the effects on pH values were small and the survival rate was not changed. SMFA also increased the serum concentrations of free fatty acids, branched-chain amino acids, ammonia, urea, and calcium. The presence of glucose enhanced or suppressed these metabolic changes. Amphibolic intermediates in the tricarboxylic acid cycle might be supplied through the catabolism of proteins in SMFA intoxication. We conclude that other factors, in addition to the accumulation of lactate, citrate, and pyruvate, may affect survival rates, and that SMFA induces imbalances in glucose, amino-acid, and, fatty-acid metabolism. All these changes are inter-related and may contribute to SMFA intoxication.

Factors associated with good self-rated health of non-disabled elderly living alone in Japan: a cross-sectional study.

BACKGROUND: Self-rated health (SRH) is reported as a reliable predictor of disability and mortality in the aged population and has been studied worldwide to enhance the quality of life of the elderly. Nowadays, the elderly living alone, a particular population at great risk of suffering physical and mental health problems, is increasing rapidly in Japan and could potentially make up the majority of the aged population. However, few data are available pertaining to SRH of this population. Given the fact that sufficient healthcare is provided to the disabled elderly whereas there is little support for non-disabled elderly, we designed this population-based survey to investigate SRH of non-disabled elderly living alone and to identify the factors associated with good SRH with the purpose of aiding health promotion for the elderly. METHODS: A cross-sectional study was conducted in a metropolitan suburb in Japan. Questionnaires pertaining to SRH and physical conditions, lifestyle factors, psychological status, and social activities, were distributed in October 2005 to individuals aged > or = 65 years and living alone. Response rate was 75.1%. Among these respondents, a total of 600 male and 2587 female respondents were identified as non-disabled elderly living alone and became our subjects. Multivariate logistic regression was used to identify the factors associated with good SRH and sex-specific effect was tested by stepwise logistic regression. RESULTS: Good SRH was reported by 69.8% of men and 73.8% of women. Multivariate logistic regression analysis showed that good SRH correlated with, in odds ratio sequence, "can go out alone to distant places", no depression, no weight loss, absence of self-rated chronic disease, good chewing ability, and good visual ability in men; whereas with "can go out alone to distant places", absence of self-rated chronic disease, no weight loss, no depression, no risk of falling, independent IADL, good chewing ability, good visual ability, and social integration (attend) in women. CONCLUSION: For the non-disabled elderly living alone, sex-appropriate support should be considered by health promotion systems from the view point of SRH. Overall, the ability to go out alone to distant places is crucial to SRH of both men and women.

Urinary fluoride reference values determined by a fluoride ion selective electrode.

As fluoride has a very short half-life in the body and the major route for fluoride excretion is via the kidney, human exposure is best measured in urine, where the concentration is expected to be highest. The urinary fluoride concentrations of 167 healthy Japanese adults were determined by means of a fluoride ion selective electrode. When the results were corrected for a specific gravity rho = 1.024 g cm-3, the histogram of urinary fluoride concentrations highly skewed toward low values with sharp peakedness (skewness = 1.56, kurtosis = 3.08). The normality of the log-transformed histogram (skewness = 0.12, kurtosis = 0.07) and the straight line on log-probability paper clearly showed a key feature of lognormal distribution of urinary fluoride. A geometric mean (GM) of 613.8 microg/l and 95% confidential interval (CI) of 241.0-1633.1 microg/l were established as reference values for urinary fluoride. The results presented in this study will be useful as guidelines for the biological monitoring of fluoride in normal subjects and individuals at risk of occupational or environmental fluoride exposure.

[Predictors of houseboundedness among elderly persons living autonomously in a rural community].

AIM: The housebound state is a risk factor for disability. This prospective study aimed to determine factors predictive of houseboundedness in the elderly, with an ultimate goal of preventing this condition. METHODS: A self-report questionnaire pertaining to mental, physical and social status was administered to 732 community-dwelling elderly persons (313 men, 419 women; age range, 65-85 years) in October 2000. All subjects independently performed both basic and instrumental activities of daily living, went out alone for long distances, and did not use long-term care insurance. They were followed up until March 2003. "Housebound" was defined as leaving the house once a week or less. A stepwise multiple logistic regression model, adjusted for age, was used to identity factors predictive of houseboundedness. Data were analyzed on the basis of gender. RESULTS: By the end of the follow-up period, 14.4% of men and 26.0% of women had become housebound. Stepwise multiple logistic regression analysis showed that predictive factors for men were lack of frequent contact with friends, neighbors and relatives; symptoms of lower limb pain; and self-assessed weight or muscle loss; and predictive factors for women were lack of frequent contact with friends, neighbors and relatives; lower limb pain; and self-assessed deterioration in health. Limited social contact and the presence of lower limb pain were common predictive factors for houseboundedness in both men and women. CONCLUSION: The findings from this study show that, among autonomous elderly persons, those who are socially isolated or who have physical pain are more likely to become housebound.

Urinary and serum titanium: assessment as an indicator of exposure to ammonium citratoperoxotitanate (IV) and its influence on renal function.

Ammonium citratoperoxotitanate IV (TAS-FINE) is a water-soluble titanium complex used to synthesize a photocatalytic titanium(IV) oxide film. This study was aimed to investigate the LD50, dose-response, time-course response, and renal toxicity of TAS-FINE using an animal model. Serum titanium (S-Ti) and its 24-h urinary excretion (U-Ti) were determined by inductively coupled plasma-argon emission spectrometry (ICPAES) after a single oral TAS-FINE administration to male Wistar rats. The LD50 of TAS-FINE was 7.97 g/kg body weight in 24 h, and its half-life was 3.78+/-1.28 d for S-Ti and 2.19+/-0.09 d for U-Ti. Although TAS-FINE was not easily absorbed in the gastrointestinal tract, it was distributed into the bloodstream in a dose-dependent manner. Within 24 h, 0.189% of administrated Ti was excreted via urine. It was speculated that TAS-FINE formed conjugates with serum constituents that resulted in nephrotoxicity resulting from an allergic reaction. The observed indices in this study were revealed to be good indicators for TAS-FINE exposure. The analytical method and animal model described in this study will help to further elucidate details about human exposure to TAS-FINE, which in recent times has become an occupational and environmental toxicant of concern.

Survey of strontium in mineral waters sold in Japan: relations of strontium to other minerals and evaluation of mineral water as a possible dietary source of strontium.

The concentrations of strontium, calcium, and magnesium in 33 brands of natural mineral waters commercially available in Japan were determined by inductively coupled plasma-atomic emission spectrometry. The geometric mean values were 94.4 microg/L for strontium, 19.1 mg/L for calcium, and 2.82 mg/L for magnesium. Wide confidence intervals of 1.96-4539 microg/L for strontium, 0.865-421 mg/L for calcium, and 0.064-123 mg/L for magnesium were observed. The significant linear relationships among the three elements over a wide distribution range suggest that the synchronized variations of these elements are regulated by the natural ecosystem and not from accidental contamination from human activities or exceptionally high natural sources. Using the results of multiple linear regression analysis, the strontium concentration can be predicted by that of calcium with the appropriate power function. The results of this study suggest that mineral water can be an important nutritional source of strontium. As trace elements imbalance is often found in older patients with chronic renal failure, we propose that close attention of trace elements intake from trendy foods or beverages is necessary to prevent this hidden problem of a rapidly aging society.

Urinary yttrium excretion and effects of yttrium chloride on renal function in rats.

Evaluation of yttrium exposure in biological samples has not been fully examined. To evaluate yttrium nephrotoxicity, yttrium chloride was orally administered to male Wistar rats and the urine volume (UV) and N-acetyl-beta-D-glucosaminidase (NAG) and creatinine excretion (Crt) were measured in 24-h urine samples. The urinary yttrium concentration and excretion rate were determined by inductively coupled plasma-argon emission spectrometry (ICP-AES). Large significant decreases of UV (>30%) and Crt (>10%) were observed at yttrium doses of 58.3-116.7 mg per rat, but no significant NAG changes was observed. This response pattern shows that a high yttrium dosage alters glomerular function rather than the proximal convoluted tubules. A urinary yttrium excretion rate of 0.216% and good dose-dependent urinary excretion (r=0.77) were confirmed. These results suggest that urinary yttrium is a suitable indicator of occupational and environmental exposure to this element, an increasingly important health issue because recent technological advances present significant potential risks of exposure to rare earth elements. We propose that the ICP-AES analytical method and animal experimental model described in this study will be a valuable tool for future research on the toxicology of rare earth elements.

Challenges and solutions in immigrant occupational health in the United States: a literature review and comparative analysis.

OBJECTIVES: Because of the declining birthrate in Japan, an increasing number of companies are hiring immigrants to fill the labor shortage. Although research on migrant occupational health has progressed in the United States, this topic has received little attention in Japan. The aim of this study was to elucidate the current situation, challenges, and solutions surrounding the occupational health of immigrant workers in the United States. METHODS: Data and selected studies were reviewed and analyzed. The results are discussed, and a few anecdotal experiences in the United States are introduced and compared. RESULTS: Possible causes of disparities in immigrant occupational health fell into the following seven categories. (Keywords for each category are shown in parentheses.) (1) Occupation (hazardous job, injury, missed workday, blue-collar worker, low birth weight); (2) Education (academic record, health literacy, training); (3) Culture (culture-specific, community-based); (4) Environment (poor hygiene, regional disparities, environmental change); (5) Access (language, statistics, workers' compensation, health insurance, voluntary restraint); (6) Infection (tuberculosis, human immunodeficiency virus/AIDS, follow-up); and (7) Discrimination (race, assault, harassment). Lack of data on immigrant workers was found to be a common problem. Some businesses and community groups achieved positive results by simultaneously dealing with multiple aforementioned categories. DISCUSSION: In the United States, the occupational health of immigrant workers has been studied mainly in terms of health disparities. Possible causes of disparities in immigrant occupational health fell into seven categories. Solutions centered on the keywords in each category were inferred. Some businesses and community groups achieved positive results by simultaneously dealing with multiple aforementioned categories. Occupational health professionals have to take each of seven categories into account to improve immigrant occupational health. Even the United States-a developed country facing many migrant occupational health problems-needs further research and better data. To address this issue in Japan, we too need more data and further research on immigrants, along with efforts by businesses and community groups.

Risk Assessment Study of Fluoride Salts: Probability-Impact Matrix of Renal and Hepatic Toxicity Markers.

The present risk assessment study of fluoride salts was conducted by oral administration of three different doses of sodium and potassium fluorides (NaF, KF) and zinc fluoride tetrahydrate (ZnF2 •4H2O) to male Wistar rats. The rats were divided into control and nine experimental groups, to which oral injections of 0.5 mL distilled water and 0.5 mL of fluoride solutions, respectively, were given. The dosage of fluoride compounds was adjusted to contain 2.1 mg (low-dose group, LG), 4.3 mg (mid-dose group, MG), and 5.4 mg fluoride per 200 g rat body weight (high-dose group, HG) corresponding to 5, 10, and 12.5 % of LD50 values for NaF. The 24-h urine volume, N-acetyl-ß-D-glucosaminidase (NAG) and creatinine clearance (Ccr) were measured as markers of possible acute renal impact. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined in serum samples as markers of acute hepatic impact. The levels of serum and urinary fluoride were determined to evaluate fluoride bioavailability. The results reveal that higher doses of NaF, KF, and ZnF2 induced renal damage as indicated by higher urinary NAG (p < 0.05 with ≥90th percentile of control). High doses of ZnF2 also induced a significant Ccr decrease (p < 0.05 with ≤10th percentile of control). Low doses of NaF and mid-doses of ZnF2 induced polyuria (p < 0.05 with ≥90th percentile of control) while medium doses of NaF and low doses of KF also induced liver damage, as indicated by a high level of AST (p < 0.05 with ≥90th percentile of control). These findings suggest that oral administration of fluoride is a potential, dose-dependent risk factor of renal tubular damage.

Comparison of the Biological Impacts of the Fluoride Compounds by Graphical Risk Visualization Map Technique.

Various fluoride compounds are widely used in industry. The present risk assessment study was conducted using a series of inorganic binary fluorides of the type XFn, where X(n) = Na(+), K(+), Li(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Al(3+), Nd(3+), La(3+), Ce(3+), Sm(3+), Gd(3+), Y(3+), Yb(2+), and Zn(2+). The aqueous solutions of these salts were orally administrated to 16 experimental groups (one for each of the salts tested). The levels of fluoride, N-acetyl-ß-D-glucosaminidase in cumulative 24-h urine samples and creatinine clearance were measured to assess possible acute renal damages. The levels of fluoride, alanine aminotransferase, and aspartate aminotransferase were also determined in serum samples to assess possible acute hepatic damages. The results reveal that sodium fluoride (NaF), potassium fluoride (KF), and zinc fluoride tetrahydrate (ZnF2 (.)4H2O) can carry the fluoride ion into the bloodstream and that it is excreted via urine more readily than the other compounds tested. These fluorides were assigned the highest risk impact factor. Most of the rare earth fluorides are insoluble in water while those groups 2 and 13 of the periodic table are slightly soluble, so that they do not have a significant negative risk. These findings suggest that the biological impact of fluoride depends on the accompanying counter ion and its solubility. The risk map obtained in the present study shows that the graphical visualization map technique employed is a valuable new tool to assess the toxicological risk of chemical compounds.

Hemodialyzability of ionizable fluoride in hemodialysis session.

The fluoride ion content in serum and in dialysate medium was determined by means of a fluoride ion-selective electrode in 29 patients undergoing hemodialysis treatment. Abnormally high serum fluoride of 65.9 +/- 28.3 microg l(-1) at the beginning and 46.5 +/- 26.7 microg l(-1) at the completion of the hemodialysis session was observed. Results showed that 60.0 +/- 23.9% of the serum fluoride at the beginning of the session was theoretically filterable, and 80.8 +/- 42.4% of this fraction was actually filtered throughout the hemodialysis session. The dialysis procedure is considered to be safe and adequate for serum fluoride removal. The high serum fluoride at the completion of the hemodialysis session was thought to originate from the fraction of unfilterable binding fluoride. To make further progress towards improvements in serum fluoride removal during HD, attention to the binding fraction of serum fluoride is required.

Log-normal distribution of the trace element data results from a mixture of stocahstic input and deterministic internal dynamics.

In previous article, we showed a log-normal distribution of boron and lithium in human urine. This type of distribution is common in both biological and nonbiological applications. It can be observed when the effects of many independent variables are combined, each of which having any underlying distribution. Although elemental excretion depends on many variables, the one-compartment open model following a first-order process can be used to explain the elimination of elements. The rate of excretion is proportional to the amount present of any given element; that is, the same percentage of an existing element is eliminated per unit time, and the element concentration is represented by a deterministic negative power function of time in the elimination time-course. Sampling is of a stochastic nature, so the dataset of time variables in the elimination phase when the sample was obtained is expected to show Normal distribution. The time variable appears as an exponent of the power function, so a concentration histogram is that of an exponential transformation of Normally distributed time. This is the reason why the element concentration shows a log-normal distribution. The distribution is determined not by the element concentration itself, but by the time variable that defines the pharmacokinetic equation.

[WHO's Framework Convention on Tobacco Control potential impact on tobacco control in Japan].

OBJECTIVE: The objective of the paper are to introduce the current global tobacco control measures undertaken by WHO and other international organizations, and to describe the impact on domestic tobacco control in Japan. METHODS: Publications and documents, mainly for WHO, were reviewed especially with reference to the Framework Convention on Tobacco Control (FCTC). RESULTS: WHO has been promotion comprehensive tobacco control globally as well as regionally in order to assist and promote its national health policy. In 1998, WHO established the Tobacco Free Initiative (TFI) to take action against the growing health impact of tobacco consumption around the world. WHO has also been proposing the FCTC, the first international convention in the health field, which includes, for example, restrictions on advertisement, selling to, or buying from persons aged under 18. Currently, the FCTC is being negotiated by governments and is expected to be ratified before May 2003. WHO is also working together with other international organizations, such as the World Bank, in synchronizing its global tobacco control policy. DISCUSSION AND CONCLUSIONS: "Smoking and health" is, without doubt, the most significant public health problem internationally and domestically. However, tobacco control tends to be less strict in Japan than in other developed countries. Even among health personnel in Japan, the health impact is still underestimated, thus its control remains partial. Accelerated public health campaigns against tobacco and health promotion activities are greatly needed. These could be carried out more effectively in the broad context of promotion of the FCTC.

Risk assessment visualization of rubidium compounds: comparison of renal and hepatic toxicities, in vivo.

Rubidium has been considered to be nontoxic. Its use includes thin film on glass deposition and as medical contrast medium. Recent technology innovations also involve the use of rubidium, but there is limited information about the biological effects of its various compounds. In the present risk assessment study, a series of rubidium compounds with different counter anions-acetate, bromide, carbonate, chloride, and fluoride-were orally administrated in a single dose to several groups of rats. Cumulative 24-h urine samples were obtained, and the levels of rubidium, fluoride, N-acetyl-ß-D-glucosaminidase and creatinine were measured to evaluate possible acute renal effects. Daily samples of serum were also obtained to determine the levels of aspartate and alanine aminotransferases to assess possible acute hepatic effects. Urinary rubidium excretion recovery of 8.0-10.5% shows that urine can be a useful diagnostic tool for rubidium exposure. The present results reveal that rubidium shows different biological effects depending on the counter anion. A pattern of large significant NAG leakage and elevation of ALT observed in rats treated with anhydrous rubidium fluoride indicates renal and hepatic toxicities that can be attributed to fluoride. The techniques reported in this study will be of help to assess the potential risks of toxicity of rubidium compounds with a variety of anions.

Urinary monitoring of exposure to yttrium, scandium, and europium in male Wistar rats.

On the assumption that rare earth elements (REEs) are nontoxic, they are being utilized as replacements of toxic heavy metals in novel technological applications. However, REEs are not entirely innocuous, and their impact on health is still uncertain. In the past decade, our laboratory has studied the urinary excretion of REEs in male Wistar rats given chlorides of europium, scandium, and yttrium solutions by one-shot intraperitoneal injection or oral dose. The present paper describes three experiments for the suitability and appropriateness of a method to use urine for biological monitoring of exposure to these REEs. The concentrations of REEs were determined in cumulative urine samples taken at 0-24 h by inductively coupled plasma atomic emission spectroscopy, showing that the urinary excretion of REEs is <2 %. Rare earth elements form colloidal conjugates in the bloodstream, which make high REEs accumulation in the reticuloendothelial system and glomeruli and low urinary excretion. The high sensitivity of inductively coupled plasma-argon emission spectrometry analytical methods, with detection limits of <2 µg/L, makes urine a comprehensive assessment tool that reflects REE exposure. The analytical method and animal experimental model described in this study will be of great importance and encourage further discussion for future studies.

[Systematic training for occupational physicians in schools of public health in the US and its application to Japan's system--Master of Public Health Program at Harvard School of Public Health].

OBJECTIVES AND RESULTS: Globalization has progressed tremendously resulting in far-reaching changes in the work environment. In Japan, occupational health and safety (OSH) activities are performed under and improved by regulations. However, this system is not likely to satisfy the unceasing diversification of social demand for OSH in recent years. The US adopts a self-imposed OSH system with responsibility carried by employers under a system of minimum regulation. This paper introduces the systematic training for occupational physicians in schools of public health in the US, which is creating a base of OSH professionals who can meet social demand. DISCUSSION: To satisfy the diverse demand for recent OSH, it is essential to improve the basic skills of occupational physicians and other OSH professionals by offering systematic training in Japan. Some examples of systematic training for occupational physicians in schools of public health in the US are discussed with the goal of improving Japan's future OSH.

Distribution, elimination, and renal effects of single oral doses of europium in rats.

Single doses of europium (III) chloride hexahydrate were orally administered to several groups of rats. Cumulative urine samples were taken at 0-24 h, and blood samples were drawn after 24-h administration. The europium concentration was determined in these samples by inductively coupled plasma atomic emission spectroscopy. The volume, creatinine, ß-2-microglobulin, and N-acetyl-ß-D-glucosaminidase were measured in the urine samples to evaluate possible europium-induced renal effects. The blood samples showed low europium distribution, with an average of 77.5 µg/L for all groups. Although the urinary concentration and excretion showed dose-dependent increases, the percentage of europium excreted showed a dose-dependent decrease, with an average of 0.31% in all groups. The administration of europium resulted in a significant decrease of creatinine and a significant increase of urinary volume, N-acetyl-ß-D-glucosaminidase, and ß-2-microglobulin. Rare earth elements, including europium, are believed to form colloidal conjugates that deposit in the reticuloendothelial system and glomeruli. This specific reaction may contribute to low europium bioavailability and renal function disturbances. Despite low bioavailability, the high performance of the analytical method for determination of europium makes the blood and urine sampling suitable tools for monitoring of exposure to this element. The results presented in this study will be of great importance in future studies on the health impacts of rare earth elements.