Solvent use in private research laboratories in Japan: comparison with the use in public research laboratories and on production floors in industries.

BACKGROUND AND OBJECTIVES: 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. MATERIALS: 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 gas-chromatographic analyses for solvents was conducted in accordance with regulatory requirements. RESULTS: 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. CONCLUSIONS: 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.

Shift to non-aromatic solvents in solvent workplaces in Japan.

OBJECTIVES: The present analyses were initiated to elucidate changes in types of prevalently used organic solvents in various solvent workplaces in Japan during the past 30 years. METHODS: Five publications on industrial solvent use were employed as databases, which were supplemented by solvent workplace surveys in 2010-2012; the surveys were conducted following regulation-stipulated procedures. In practice, data on 500-600 unit workplaces/year were available; the data were classified by types of solvent work according to the regulation. RESULTS: The use of aromatic solvents (typically toluene) has been gradually replaced in a recent few years with methyl alcohol and isopropyl alcohol in surface coating workplaces, whereas toluene has been essentially most prevalent in printing and painting workplaces. In cleaning workplaces, the use of chlorinated hydrocarbon solvents was almost terminated in the years before 2000. CONCLUSIONS: The present study may be the first report to note that the prevalence of toluene use has been decreasing in surface coating workplaces to be replaced by alcohols, although toluene has been most prevalent in printing and painting workplaces. In cleaning workplaces, there was a substantial reduction in the use of chlorinated hydrocarbon solvents.

Use of organic solvents in large research institutions in Japan.

OBJECTIVES: Laboratories in research institutions use organic solvents in research and development. Nevertheless, the types of solvents in use have been seldom reported. This study was initiated to elucidate types of organic solvents used in large research institutions in Japan, with a focus on possible different use among research fields. METHODS: In 2010-2011, 4517 laboratories in seven large research institutions were visited. In accordance with legal stipulations, air in each laboratory was collected in polyvinyl fluoride bags and analyzed by direct injection into a gas-chromatograph for 47 types of organic solvents. In evaluation, the laboratories were grouped by 5 research fields, i.e., agriculture, biology, medicine, natural science, and technology and engineering. RESULTS: Types of organic solvents commonly used in research activities were not diverse. Those commonly used were chloroform and 1,2-dichloroethane out of 7 Group 1 organic solvents (with high toxicities); 6 organic solvents, i.e., acetone and methyl alcohol in general, ethyl acetate, hexane and toluene in technology and engineering laboratories; and xylenes in medical fields out of 40 Group 2 organic solvents (with relatively low toxicities). Judging from solvent vapor concentrations, work environments in more than 99 % of laboratories were considered adequate. Nevertheless, use of chloroform in high-performance liquid chromatography (HPLC) resulted in inadequate environments in 30 laboratories (0.7 %). CONCLUSIONS: Organic solvents commonly used were not very diverse. Work environments in research laboratories were generally good, but the environment with use of chloroform in HPLC analysis remained yet to be improved.

Organic solvent use in enterprises in Japan.

This study was initiated to elucidate possible changes in types of organic solvents (to be called solvents in short) used in enterprises in Japan through comparison of current solvent types with historical data since 1983. To investigate current situation in solvent use in enterprises, surveys were conducted during one year of 2009 to 2010. In total, workroom air samples in 1,497 unit workplaces with solvent use were analyzed in accordance with regulatory requirements. Typical use pattern of solvents was as mixtures, accounting for >70% of cases. Adhesives spreading (followed by adhesion) was relatively common in small-scale enterprises, whereas printing and painting work was more common in middle-scale ones, and solvent use for testing and research purpose was basically in large-scaled enterprises. Through-out printing, painting, surface coating and adhesive application, toluene was most common (being detected in 49 to 82% of workplaces depending on work types), whereas isopropyl alcohol was most common (49%) in degreasing, cleaning and wiping workplaces. Other commonly used solvents were methyl alcohol, ethyl acetate and acetone (33 to 37%). Comparison with historical data in Japan and literature-retrieved data outside of Japan all agreed with the observation that toluene is the most commonly used solvent. Application of trichloroethylene and 1,1,1-trichloroethane, once common in 1980s, has ceased to exist in recent years.

Organic solvent use in research institutions in Japan.

In 2008-2009, types of organic solvents used and air-borne vapor concentrations were surveyed in 1909 laboratories in four large research institutions in accordance with current regulations. The results were classified into 5 groups in terms of research fields (agriculture, biology, medicine, natural science, and technology and engineering) and evaluated after the regulatory rules. Laboratory air analyses by gas chromatography identified 5 and 20 solvents out of 7 Group 1 solvents and 40 Group 2 solvents, respectively; 10 solvents were used in more than 10% of the laboratories in each of the 5 research fields. The use of unmixed single solvent appeared to be unique in research laboratories in contrast to use of solvent mixtures in industrial facilities for production. Laboratories of technology and engineering fields used more various organic solvents more frequently, whereas use of xylenes appeared to be more specific to laboratories of bio-medical fields. Among the commonly used solvents, chloroform was the leading solvent to induce poorer results in regulatory classification (i.e., Class 3 in Administrative Control Classes) typically when applied in high pressure liquid chromatography which was too voluminous to be accommodated in a local exhaustion chamber.

Validation of urine density correction in cases of hippuric acid and un-metabolized toluene in urine of workers exposed to toluene.

To investigate if it is appropriate to apply urine density correction when a urine sample is dense or dilute. Data on hippuric acid (HA-U), toluene (Tol-U), creatinine (CR) and specific gravity (SG) in end-of-shift urine samples and exposure to air-borne toluene were cited from previous publications. In practice, 837 cases were available, and they were classified into dense, intermediate and dilute groups taking 0.3 and 3.0 g/l of CR and 1.010 and 1.030 of SG as cut-off points. Lines of regression of HA-U and Tol-U (as observed, CR-corrected or SG-corrected) with air-borne toluene were calculated for each density groups, and correlation coefficients (CCs) were compared. The dense groups gave CCs similar to those of the intermediate groups. Dilute versus intermediate group comparison also gave promising results. These conclusions were however based primarily on the findings with observed values, because the numbers of cases in the dilute or dense group were limited when CR- or SG-correction was applied. Literature survey showed that urine density correction does not always improve the correlation between solvents in air and exposure makers in urine. It was concluded that no correction for urine density may be necessary in evaluating HA-U and Tol-U in dense (and probably also dilute) urine samples as markers of occupational toluene exposure. Just in case when correction for urine density is desired for any reason, SG-correction may be recommended.

Limited validity of o-cresol and benzylmercapturic acid in urine as biomarkers of occupational exposure to toluene at low levels.

This study was initiated to evaluate o-cresol and benzylmercapturic acid in urine in comparison with other biomarkers, as tools to estimate the intensity of occupational exposure to toluene at low levels. In total, 108 solvent exposed workers (engaged in tape production) and 17 non-exposed controls (all men) participated in the study. The surveys were conducted in the second half of working weeks. Diffusive sampling was conducted to measure 8-h time-weighted average intensity of occupational exposure to toluene. Blood and urine samples were collected at the end of a working shift. Blood samples were subjected to analysis for toluene (Tol-B), and urine samples were analyzed for benzyl alcohol (BeOH-U), benzylmercapturic acid (BMA-U), o-cresol (o-CR-U), hippuric acid (HA-U) and toluene (Tol-U) by the methods previously described. The toluene concentrations in workplaces were low in general, with a geometric mean (GM) and the maximum concentration of 1.9 ppm and 8.8 ppm, respectively. The statistical analyses of the six biomarkers for correlation with air-borne toluene showed that both Tol-B and Tol-U gave a high correlation coefficient of 0.58 to 0.61 (p<0.01), whereas the coefficients for BeOH-U and BMA-U together with HA-U were all low (up to 0.22, depending on the correction for urine density) and statistically insignificant (p>0.10) in most cases. o-CR-U had an intermediary coefficient of 0.20 (p<0.05). Comparison with previous publications disclosed that BeOH-U, BMA-U and HA-U correlate with toluene in air when the exposure is intense (e.g., 50 ppm or above), but no longer proportional to air-borne toluene when the exposure is low, e.g., 2 ppm. Such appeared to be also the case for o-CR-U. In over-all evaluation, the validity of o-CR-U in monitoring occupational exposure to toluene at low levels (e.g., 2 ppm) appear to be limited, and BMA-U is not an appropriate biomarker. BeOH-U and HA-U are also inappropriate for this purpose. Only Tol-B and Tol-U may be employed to estimate toluene exposure at low levels.

Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene.

This study was initiated to identify a marker of choice to monitor occupational exposure to toluene through quantitative evaluation of changes in correlation coefficients (CCs), taking advantage of a large database. Six known or proposed exposure markers in end-of-shift blood (B) and urine (U) were studied, i.e., toluene in blood (Tol-B) and benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and toluene in urine (BeOH-U, BMA-U, o-CR-U, HA-U, and Tol-U, respectively). To construct a database, data on 8-h time-weighted average intensity of occupational exposure to toluene and resulting levels of the six exposure markers in blood or urine were cited for 901 cases from previous four publications of this study group and combined with 146 new cases. In practice, 874 cases (all men) were available when extremely dilute or dense urine samples were excluded. The 874 cases were classified taking the upper limit (from 120 ppm to 1 ppm) of the toluene exposure concentration, and the CCs for the six markers with TWA toluene exposure intensity were calculated. For further evaluation, the 874 cases were divided into 10 per thousand in terms of TWA toluene exposures, and several 10 per thousand were combined so that sufficient numbers of cases were available for calculation of the CCs at various levels of toluene exposure. Perusal was made to know whether or not and which one of the six makers gave significant CC even at low level of toluene exposure. The CCs for BMA-U, o-CR-U and HA-U with TWA toluene exposure were well >0.7 when toluene exposure was intense (e.g., up to 60-100 ppm as the upper limit of the exposure range), but were reduced when the upper limit of toluene exposure was less than 50 ppm, and the CCs were as small as <==0.2 when the upper limit was about 10 ppm or less. In contrast, Tol-U and Tol-B were correlated with exposure to toluene down to the 0.4 when the cases in the 60th-100th per thousand were examined. The CCs for Tol-U and Tol-B were >0.3 also for cases in the 0th-60th or 30th-70th per thousand, whereas the CCs for other four markers were <0.3. In over-all evaluation, it was concluded that HA and o-CR are among the markers of choice to monitor occupational toluene exposure at high levels, and that only un-metabolized toluene in urine or in blood is recommended when toluene exposure level is low (e.g., 10 ppm or less). Toluene in urine may be preferred rather than that in blood due to practical reasons, such as non-invasiveness.

Chemical exposures in research laboratories in a university.

Research laboratories in a university were investigated for air-borne levels of legally designated organic solvents and specified chemical substances. Repeated surveys in 2004-5 (four times in the two years) of about 720 laboratories (thus 2,874 laboratories in total) revealed that the solvent concentrations were in excess of the Administrative Control Levels only in a few laboratories (the conditions improved shortly after the identification) and none with regard to specified chemicals. Thus, working environments were in Control Class 1 in almost all (99.5%) laboratories examined. Such conditions were achieved primarily by extensive installation and use of local exhaust systems. The survey further revealed that types of chemicals used in research laboratories were extremely various (only poorly covered by the regulation) whereas the amounts of each chemical to be consumed were quite limited. For protection of health of researchers (including post- and under-graduate students) in laboratories, therefore, it appeared more appropriate to make personal exposure assessment rather than evaluation of levels of chemicals in air of research laboratories. Considering unique characteristics of research activity, it is important to educate each researcher to make his/her own efforts to protect his/her health, through supply of knowledge on toxicity of chemicals as well as that on proper use of protective equipments including exhaust chambers.

Evaluation of biomarkers of occupational exposure to toluene at low levels.

OBJECTIVES: The purpose of the present study was to compare validity of various biomarkers of occupational exposure to toluene (Tol) at low levels. The focus was placed on the comparison of un-metabolized toluene in urine (Tol-U) and peripheral blood (Tol-B) with hippuric acid in urine (HA-U). METHODS: Surveys were conducted in 16 workplaces on the second half of working weeks, with participation of male solvent workers. Urine and peripheral blood samples were collected at the end of the shifts. After exclusion of cases with dense or diluted urine samples, 473 valid sets of samples were obtained for statistical evaluation. Time-weighted average exposure (for about 8-h) were monitored by diffusive sampling for toluene and other four solvents. Blood samples were subjected to the analyses for Tol-B, whereas urine samples were analyzed for HA-U and Tol-U. RESULTS: The solvent exposures were low, i.e., a grand geometric mean (GM) Tol concentration was 1.6 ppm, and the GM for the SUM in the additiveness equation was 0.12. The correlation analyses of the biomarkers in urine and blood with Tol exposure showed that Tol-U and Tol-B were more closely [correlation coefficients (r) being 0.67 and 0.60, respectively] related than HA-U (r = 0.27). Results of receiver operator characteristic analyses were in agreement with the correlation analysis results. CONCLUSIONS: Taking the non-invasive nature of sampling together, Tol in the end-of-shift spot urine sample appears to be the marker of choice for biological monitoring of occupational exposure to Tol at low levels such as <2 ppm as a geometric mean.

Comparative evaluation of biomarkers of occupational exposure to toluene.

OBJECTIVES: This study was initiated to make comparative evaluation of five proposed urinary markers of occupational exposure to toluene, i.e., benzyl alcohol, benzylmercapturic acid, omicron-cresol, hippuric acid and un-metabolized toluene. METHODS: In practice, six plants in Japan were surveyed, and 122 Japanese workers (mostly printers; all men) together with 12 occupationally nonexposed control subjects (to be called controls; all men) agreed to participate in the study. Surveys were conducted in the second half of working weeks. Time-weighted average exposure (about 8 h) to toluene and other solvents were monitored by diffusive sampling. End-of-shift urine samples were collected and analyzed for the five markers by the methods previously described; simultaneous determination of omicron-cresol was possible by the method originally developed for benzyl alcohol analysis. RESULTS: The toluene concentration in the six plants was such that the grand geometric mean (GM) for the 122 cases was 10.4 ppm with the maximum of 121 ppm. Other solvents coexposed included ethyl acetate (26 ppm as GM), methyl ethyl ketone (26 ppm), butyl acetate (1 ppm) and xylenes (1 ppm). By simple regression analysis, hippuric acid correlated most closely with toluene in air (r = 0.85 for non-corrected observed values) followed by un-metabolized toluene (r = 0.83) and o-cresol (r = 0.81). In a plant where toluene in air was low (i.e., 2 ppm as GM), however, un-metabolized toluene and benzylmercapturic acid in urine showed better correlation with air-borne toluene (r = 0.79 and 0.61, respectively) than hippuric acid (r = 0.12) or o-cresol (r = 0.17). Benzyl alcohol tended to increase only when toluene exposure was intense. Correction for creatinine concentration or specific gravity of urine did not improve the correlation in any case. Multiple regression analysis showed that solvents other than toluene did not affect the levels of omicron-cresol, hippuric acid or un-metabolized toluene. Levels of benzylmercapturic acid and un-metabolized toluene were below the limits of detection [limit of detections (LODs); 0.2 and 2 microg/l, respectively] in the urine from the control subjects. CONCLUSIONS: In over-all evaluation, hippuric acid, followed by un-metabolized toluene and omicron-cresol, is the marker of choice for occupational toluene exposure. When toluene exposure level is low (e.g., 2 ppm), un-metabolized toluene and benzylmercapturic acid in urine may be better indicators. Detection of un-metabolized toluene or benzylmercapturic acid in urine at the levels in excess of the LODs may be taken as a positive evidence of toluene exposure, because their levels in urine from the controls are below the LODs. The value of benzyl alcohol as an exposure marker should be limited.

Benzyl alcohol as a marker of occupational exposure to toluene.

Benzyl alcohol (BeOH) is a urinary metabolite of toluene, which has been seldom evaluated for biological monitoring of exposure to this popular solvent. The present study was initiated to develop a practical method for determination of BeOH in urine and to examine if this metabolite can be applied as a marker of occupational exposure to toluene. A practical gas-liquid chromatographic method was successfully developed in the present study with sensitivity low enough for the application (the limit of detection; 5 microg BeOH /l urine with CV=2.7%). Linearity was confirmed up to 10 mg BeOH/l, the highest concentration tested, and the reproducibility was also satisfactory with a coefficient of variation of 2.7% (n=10). A tentative application of the method in a small scale study with 45 male workers [exposed to toluene up to 130 ppm as an 8-h time-weighted average (8-h TWA)] showed that BeOH in the end-of-shift urine samples was proportional to the intensity of exposure to toluene. The calculated regression equation was Y=50+1.7X (r=0.80, p<0.01), where X was toluene in air (in ppm as 8-h TWA) and Y was BeOH in urine (in microg/l of end-of-shift urine). The levels of BeOH in the urine of the non-exposed was about 50 microg/l, and ingestion of benzoate as a preservative in soft drinks did not affect the BeOH level in urine. The findings as a whole suggest that BeOH is a promising candidate for biological monitoring of occupational exposure to toluene.

Relation of average and highest solvent vapor concentrations in workplaces in small to medium enterprises and large enterprises.

The present study was initiated to examine the relationship between the workplace concentrations and the estimated highest concentrations in solvent workplaces (SWPs), with special references to enterprise size and types of solvent work. Results of survey conducted in 1010 SWPs in 156 enterprises were taken as a database. Workplace air was sampled at > or = 5 crosses in each SWP following a grid sampling strategy. An additional air was grab-sampled at the site where the worker's exposure was estimated to be highest (estimated highest concentration or EHC). The samples were analyzed for 47 solvents designated by regulation, and solvent concentrations in each sample were summed up by use of additiveness formula. From the workplace concentrations at > or = 5 points, geometric mean and geometric standard deviations were calculated as the representative workplace concentration (RWC) and the indicator of variation in workplace concentration (VWC). Comparison between RWC and EHC in the total of 1010 SWPs showed that EHC was 1.2 (in large enterprises with>300 employees) to 1.7 times [in small to medium (SM) enterprises with < or = 300 employees] greater than RWC. When SWPs were classified into SM enterprises and large enterprises, both RWC and EHC were significantly higher in SM enterprises than in large enterprises. Further comparison by types of solvent work showed that the difference was more marked in printing, surface coating and degreasing/cleaning/wiping SWPs, whereas it was less remarkable in painting SWPs and essentially nil in testing/research laboratories. In conclusion, the present observation as discussed in reference to previous publications suggests that RWC, EHC and the ratio of EHC/WRC varies substantially among different types of solvent work as well as enterprise size, and are typically higher in printing SWPs in SM enterprises.

Green chemistry in urinalysis for trichloroethanol and trichloroacetic acid as markers of exposure to chlorinated hydrocarbon solvents.

The aim of the present study was to develop a method of urinalysis for trichloroacetic acid (TCA) and trichloroethanol (TCE), and therefore total trichloro-compounds (TTC) as the sum, with least use of hazardous chemicals, being green in that sense. After acid hydrolysis followed by dilution with an ethanol (EtOH)-methanol (MeOH)-water mixture, capillary gas-choromatography with an electron-capture detector can quantify TCA and TCE in the diluted hydrolyzate. Comparison studies showed that the results were identical among three methods, i.e., 1. the method developed in the present study, 2. a head-space GC with acid hydrolysis of conjugated TCE and methyl-esterification of TCA, and 3. traditional colorimetry with Fujiwara reaction. When applied to exposure-excretion analysis, the three methods gave results reproducible to each other. Over-all evaluation therefore was such that the method developed in the present study is as equally reliable as previously developed methods. It should be further noted that the procedures are very simple, with minimum use of occupationally or environmentally hazardous chemicals. In case the determination of only TCA is requested, it is possible to skip the hydrolysis step so that the treatment prior to the GC analysis is even simpler, i.e., just a 60-fold dilution of the urine sample with the EtOH-MeOH-water mixture. It was also demonstrated that correction of urinary analyte levels for urine density in terms of creatinine or specific gravity did not improve the correlation with the intensity of TRI exposure.

Field survey on types of organic solvents used in enterprises of various sizes.

OBJECTIVE: To examine (1) common types of organic solvent work and prevalent types of solvent used, and (2) possible association of high solvent concentration with types of solvent work and with enterprise size. METHODS: The present survey was conducted in Kyoto, Japan, in April 2004 to March 2005. Air samples were collected in 1,010 solvent workplaces (SWPs) (>or=5 samples/SWP) in 156 enterprises of various sizes, and analyzed for 47 legally designated organic solvents by flame-ionization detector-equipped gas-liquid chromatography. The geometric mean value of the concentrations (after summation by use of the additiveness formula) in the >or=5 samples were taken as a representative value for the SWP. Solvent works were classified into 11 categories according to the Japanese regulation. Enterprises were classified in terms of number of employees. RESULTS: Degreasing (including cleaning and wiping) was the most common type of solvent work, followed by painting and printing, and toluene was the most often detected solvent (i.e., in 42% of the 1,010 SWPs). Further observation by types of solvent work disclosed that toluene was most common in printing (61%), painting (78%), and adhesive spreading/adhesion SWPs (47%), whereas isopropyl alcohol was the leading solvent in cases of surface coating (51%) and degreasing/cleaning/wiping SWPs (42%). Use of methyl alcohol was also high (36% of all cases). In contrast, use of hexane in adhesives was limited (12%). There was a reverse size-dependency in solvent concentrations in air of SWPs, being five times higher in enterprises with or=501 employees. Among SWPs, concentrations tended to be high in printing workplaces especially in small enterprises. In contrast, the levels were much lower in testing and research laboratories irrespective of enterprise size. Comparison with the results in a previous survey in 1996 (Ukai et al. 1997) showed that use of toluene and xylenes was reduced and use of isopropyl alcohol and methyl alcohol was increased. The need of continuous updating of the target analyte list was stressed in relation to the limitation of the present study. CONCLUSIONS: Solvent levels were about five times higher in small enterprises as compared with the levels in large enterprises. There was a gradual shift in solvent use from aromatics to other solvents, typically alcohols. The use of hexane in adhesives was reduced. Solvent levels were relatively high in solvent-drying and printing workplaces and low in degreasing/cleaning/wiping workplaces and testing/research laboratories.

Comparison of colorimetric and HPLC methods for determination of delta-aminolevulinic acid in urine with reference to dose-response relationship in occupational exposure to lead.

Both traditional colorimetry and recently developed HPLC-fluorometry have been in use for determination of delta-aminolevulinic acid in urine (ALA-U), an effect marker of occupational exposure to lead (Pb). The present study was initiated to compare the values by the two methods on an epidemiology basis among workers occupationally exposed to lead (Pb), to estimate quantitatively the colorimetry-associated increment over the values by the HPLC method, to evaluate ALA-U determination in occupational health service for Pb-exposed workers, and to identify a critical Pb-B to induce an elevation in ALA-U. For this purpose, blood and urine samples were collected from three groups of Pb-exposed workers (both men and women in combination, including smokers) and analyzed for Pb in blood (Pb-B; measured in all subjects) and ALA-U (by colorimetry or HPLC), i.e., Group 1 (164 subjects with urinalysis by the two methods), Group 2 (2,923 subjects by colorimetry), and Group 3 (2,540 subjects by HPLC). ALA-U when measured by colorimetry was higher than the values by HPLC, and that the mean difference on a group basis was 1.4 mg/l (in a range of 1.1 to 1.8 mg/l), irrespective of Pb-B levels. It was also found that the increase in ALA-U was small when Pb-B was relatively low (e.g., < or = 40 microg/100 ml), and that the increase on a group basis in response to an increase in Pb-B from 5 to 40 microg/100 ml was as small as < or = 0.6 mg/l. Thus, ALA-U appeared to be not a sensitive marker of Pb effects at low Pb-B levels. ALA-U however increased substantially with a point of inflection at the Pb-B level of about 17-34 microg/100 ml. Thus it was concluded that ALA-U as measured by colorimetry is greater than ALA-U by HPLC by 1.4 mg/l on average irrespective of intensity of Pb-exposure, which may induce bias in evaluation of health effect, and that ALA-U levels will increase when Pb-B is in excess of 17-34 microg/100 ml.

The threshold cadmium level that causes a substantial increase in beta2-microglobulin in urine of general populations.

Cadmium (Cd) is a toxic element ubiquitous in the environment, and general populations have been exposed to this element primarily via foods. Thus, the critical level of non-occupational Cd exposure to cause any health effects among general populations is of public health as well as toxicological concern. The objectives of the present study were to examine the quantitative relationship between cadmium (Cd-U) and beta2-microglobulin in urine (beta2-MG-U) as a marker of exposure to Cd and as a marker of renal tubular dysfunction, respectively, and to identify a threshold Cd-U, if present, in causing a substantial increase in beta2-MG-U. Thus, paired data on geometric mean (GM) Cd-Ucr (i.e., Cd-U as corrected for creatinine [cr] concentration) and GM beta2-MG-Ucr (beta2-MG-U as corrected for cr) of residents in polluted as well as nonpolluted areas in Japan were retrieved in international and domestic sources. In practice, 245 cases of the data pairs were obtained in 51 articles published since 1975. Statistical analysis on ordinary scales disclosed that beta2-MG-Ucr increased markedly when Cd-Ucr exceeded a certain level. The relation between the two parameters after double-logarithmic conversion was in a shape of the letter J or a stick for ice hockey. Analysis for Cd-Ucr at the flexion point gave Cd-Ucr of 4 (on double logarithmic scales) or 7 microg/g cr (on ordinary scales). Cd-Ucr levels that correspond to a beta2-MG-Ucr of 1,000 microg/g cr were estimated to be 8-9 microg/g cr, by ordinary and logarithmic assumption as well as by the 3rd degree regression analysis. Thus, it is concluded that there is a threshold Cd-Ucr level that leads to a substantial increase in beta2-MG-Ucr, and that the threshold level is greater than 4 microg/g cr.

Lead levels in urine of never-smoking adult women in non-polluted areas in Japan, with references to cadmium levels in urine.

The present study was initiated to assess current level of general population exposure to lead (Pb) in terms of Pb in urine (Pb-U). For this purpose, spot urine samples were collected from 2,332 never-smoking adult women in 10 areas all-over Japan, and were subjected to analysis for Pb-U by graphite furnace atomic absorption (GFAA). Data on cadmium in urine (Cd-U) as measured by GFAA were cited from a previous publication). The grand geometric means (GM) for Pb-U as observed, as corrected for creatinine (cr) and as corrected for a specific gravity of 1.016 were 1.06 microg/l, 1.28 microg/g cr and 1.14 microg/l, respectively, with small intra- and inter-variations with geometric standard deviations of about 2 or less. Arithmetic means of the 10 GMs (one each for the 10 areas) were 1.05 microg/l, 1.19 microg/g cr and 1.18 microg/l, respectively. The levels observed appeared to be lower than levels reported for other populations in the world. Chronological comparison within Japan suggested a gradual decrease in Pb-U in past over 20 yr. No close correlation was detected between Pb-U and Cd-U.

Lower vapor concentrations in solvent workplaces in larger-scale enterprises than in smaller-scale enterprises, and exceptions.

The aim of the present study was to investigate the relationship between environmental vapor concentrations in organic solvent workplaces and size of enterprises, and to examine if occupational hygiene conditions were better in larger-scale enterprises. For this purpose, a total of 3,567 solvent workplaces were surveyed for environmental solvent vapor concentrations in 1999 to 2002. The results were classified by the size of enterprises (taking the number of employees as an indicator) and by the type of solvent work. It was observed that the vapor concentration in a typical small-scale enterprise was approximately three times as high as that in the large-scale enterprise, although the administrative control levels were not exceeded in general. The proportion of testing and research work (with less use of organic solvents and thus low vapor concentrations) among all solvent workplaces was higher in large-scale enterprises than in small-scale enterprises. The vapor concentrations in this type of workplace did not differ however irrespective of the enterprise size. Further comparison in various types of solvent workplaces disclosed similar size-dependent difference in workplaces for degreasing, cleaning, wiping, printing, and surface coating. In painting and solvent-drying work, in contrast, there was no difference in environmental concentration regardless of the size of enterprises, possibly because environmental improvement of this type of workplaces was technically more difficult than others. Thus, it was concluded that large-scale enterprises generally had better control of work environments than small-scale enterprises, with possible exceptions of painting work and solvent-drying work.

Effects of iron-deficiency anemia on cadmium uptake or kidney dysfunction are essentially nil among women in general population in Japan.

In the present study, 1476 adult women in 6 prefectures in Japan volunteered to offer peripheral blood and spot urine samples, and to complete questionnaires on social habits and health. Blood samples were analyzed for iron, ferritin and TIBC in serum in addition to RBC, Hb and Cd in whole blood. Urine samples were analyzed for Cd, alpha1-MG, and beta2-MG; the measures were corrected for creatinine and were expressed as e.g., Cd-Ucr. Among 1212 never-smokers, 37 women with < 25 ng ferritin/ml serum and < 10 g Hb/100 ml blood were classified as the anemics, whereas 701 women with > or = 25 ng/ml ferritin and > or = 10 g/100 ml Hb were taken as controls. Matching by age and the prefecture of residence was successful for 34 anemics. Comparison (by paired t-test) of Cd in blood, and Cd, alpha1-MG and beta2-MG in urine (as corrected for creatinine) of the anemics with that of matched controls showed no significant differences. Thus, it appeared likely that the current level of iron insufficiency among general women population in Japan may not induce substantial increase in Cd absorption or Cd-associated kidney dysfunction.