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Dimethylarsinic acid (DMAA) is a major metabolite of inorganic arsenicals in mammals. In the present study, we investigated its promoting effects on urinary bladder carcinogenesis in NCI-Black-Reiter (NBR) rats, which lack alpha2u-globulin synthesizing ability. Male 9-14-week-old NBR rats were treated sequentially with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 4 weeks and then given 100 ppm DMAA in their drinking water (group 1) for 32 weeks. Induction of preneoplastic lesions (papillary or nodular hyperplasia) in this DMAA-treated group was significantly increased as compared to the carcinogen alone control group (P < 0.01). The development of carcinomas was also enhanced and a significant increase in the 5-bromo-2'-deoxyuridine (BrdU) labeling index of the urinary bladder epithelial cells was observed for the DMAA treatment group. These results indicate that DMAA has promoting effects on urinary bladder carcinogenesis even in NBR rats, so its effects are not dependent on the presence of alpha2u-globulin.

A survey of solvent was conducted for 196 unit work areas in 95 plants in 1994 to 1996 in Hiroshima Prefecture, Japan. The survey had been repeated every 6 months (i.e., twice a year) during the 3-year period. Sampling and analysis of the solvent vapors were carried out after national protocols set by the regulation. Toluene was most frequently detected regardless of the type of solvent work (except for degreasing), whereas the second- and the third-most common solvents varied depending on the type of solvent works. Among chlorinated hydrocarbon solvents for degreasing, dichloromethane was most widely used. Solvent concentrations were generally low as none of the median concentrations exceeded corresponding Administrative Control Levels set by the regulation, either individually or even when the assumption of additiveness was applied. Among the 1176 cases analyzed, 80% of the unit work areas were evaluated as adequate (i.e., classified as Class I). Furthermore, about 57% stayed in Class I throughout the 3 years, suggesting that solvent exposure conditions were generally quite stable. In regulatory evaluation by classification, A-sampling was decisive in most cases, whereas the role of B-sampling was limited.

The metabolism of arsenic compounds in rats was studied by comparing urinary metabolites of arsenic compounds administered for 1 wk or 7 mo. Male F344/DuCrj rats were given 100 mg As/L as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), trimethylarsine oxide (TMAO), or arsenobetaine (AsBe), or 10 mg As/L as arsenite [As(III)] via drinking water for 7 mo. Urine was collected by forced urination after 1 wk or 7 mo. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry. In the case of As(III) ingestion, a small portion of all arsenic excreted in urine (about 6%) was excreted in inorganic form, while most arsenic was excreted as methylated arsenic metabolites. Following MMA treatments for 1 wk or 7 mo, the predominant products excreted were unchanged MMA and DMA accompanied by small amounts of TMAO and tetramethylarsonium (TeMA). In the case of DMA treatment the urinary compounds found were mainly the parent DMA and TMAO with minute amounts of TeMA. TMAO was methylated to TeMA to a slight extent after 1 wk and 7 mo of administration, although most TMAO was excreted in the form of unchanged TMAO. AsBe was predominantly eliminated in urine without any transformation. Two unidentified metabolites were detected in urine after 7 mo of arsenic species exposure; the amounts of these metabolites increased in the order DMA > MMA > TMAO with only small quantities of these detected in the As(III)-treated group. These results suggest that these unidentified metabolites are formed during a demethylation process, and not during methylation. Our findings indicate that long-term exposure to As(III), MMA, or DMA decreases the proportion of TMAO elimination in urine and increases that of DMA, M-1, and M-2, and that further methylation to TMAO to TeMA does occur to a slight extent following long-term exposure to arsenical compounds in rats.

We investigated the cytogenetic effects of dimethylarsinic acid (DMA), which is the major metabolite of inorganic arsenic compounds, on mouse bone marrow cells after a single intraperitoneal injection to mice. DMA increased mitotic indices significantly at 16, 24 and 48 h after injection, and prolonged the average generation time 1.5 h at the 24 h. These results suggest that DMA may cause mitotic arrest in vivo as well as in vitro. However the activity of mitotic arrest induced by DMA was much weaker than that induced by colchicine. Metaphase cells obtained after administration of DMA without colchicine pretreatment were morphologically normal except for chromosome number, which varied by stage from the prophase to the telophase in M phase as seen after administration of saline. DMA significantly induced aneuploids. The frequencies of euploids with DMA and saline treatment were 55.1 and 94.0%, respectively, and in DMA treatment hyperploids with 1 or 2 extra chromosomes were over 80% of all aneuploids. These results suggest that aneuploidy induced by DMA might be associated with carcinogenicity of arsenic.

Phthalic anhydride (PA), used in the chemical industry, binds to proteins and causes allergic reactions. It is important to study the characteristics of antibody to PA-protein. We produced specific IgG against PA-rabbit serum albumin (RSA) by administering subcutaneous injections of PA-RSA conjugate to two rabbits. Both rabbits' sera had high titers of IgG not only to PA-RSA but also to PA-human serum albumin (HSA) and HSA. In enzyme-linked immunosorbent assay (ELISA) and ELISA HSA inhibition, specific IgG to PA-HSA revealed cross-reactivity to three other phthalyl anhydride conjugates, hexahydrophthalic anhydride (HHPA)-HSA, methylhexahydrophthalic anhydride (MHHPA)-HSA, and methyltetrahydrophthalic anhydride (MTHPA)-HSA, in both sera. Titers of IgG to HHPA-HSA, MHHPA-HSA, and MTHPA-HSA were not significantly different. On affinity chromatography, highly specific IgG to PA hapten alone was purified. In the serum not binding to PA column, specific IgG to PA-HSA was significantly less than in original serum, but levels of specific IgG to other phthalyl anhydride-HSA were unchanged. Rabbits immunized with PA-RSA produced at least two types of IgG: one is to PA hapten alone and the other may be against new antigenic determinants (NADs) on HSA.

The modifying effects of dimethylarsinic acid (DMA), the major metabolite of ingested arsenicals in most mammals, on chemical carcinogenesis were investigated using rat in vivo models and reviewed here. In a multi-organ bioassay, rats pretreated with 5 carcinogens were administered DMA at various concentrations in their drinking water. Significantly increased tumor induction due to DMA was observed in the urinary bladder, kidney, liver, and thyroid gland. This was associated with significantly elevated ornithine decarboxylase activity in the kidneys of DMA-treated animals. To estimate the hazard levels of its promoting influence, further examinations were carried out concerned with urinary bladder and liver carcinogenesis. Doses of 25 and 50 ppm, respectively, of DMA were found capable of enhancing lesion development in the two organs. In conclusion, our data indicate that DMA is a carcinogen or promoter in the urinary bladder, liver, kidney and thyroid gland, in line with previous epidemiological findings.

The biotransformation following oral administration of dimethylarsinic acid (DMA), an organoarsenical herbicide and the main metabolite of inorganic arsenic in mammals, was studied in rats. Male F344/DuCrj rats were administered a single dose of DMA (50 mg/kg) orally. Urine was collected at 0, 2, 4, 8, 10, 24, and 48 h after administration by forced urination. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry (IC-ICP-MS). The proportions of urinary elimination of DMA, trimethylarsine oxide (TMAO), methylarsonic acid (MMA), an unidentified arsenic metabolite, and arsenite were determined at various timepoints after administration. Unmetabolized DMA was the most common form excreted during the first 4 h. Thereafter, a gradual decrease in the proportion of DMA was observed, while progressive increases in those of TMAO, the unidentified metabolite, and arsenite occurred. The proportion of TMAO excreted amounted to over 50% of all arsenic in urine between 6 and 24 h. The proportion of the unidentified metabolite and arsenite were each approximately 10% at 10 and 24 h after administration. The findings indicate that DMA administered to rats was initially excreted as unchanged DMA, and later as the methylated metabolite, TMAO. Arsenite, a demethylated metabolite of DMA, also was excreted later than elimination of DMA and TMAO. The hypothesis of demethylation by intestinal microorganisms can be supported by comparing the metabolites following oral and intraperitoneal administration. The unidentified metabolite was readily decomposed by HCl but was left unchanged by NaOH; these findings suggest that it was present in a complexed form in urine.

Arsenic is a human carcinogen. On the other hand, selenium supplementation can inhibit induction of carcinogenesis by chemical carcinogens. The effect of selenium compounds on the cytotoxicity of dimethylarsinic acid (DMA) and on the induction of tetraploidy by DMA were studied using Chinese hamster V79 cells. Two selenium compounds were tested, sodium selenite and trimethylselenonium iodide (TMSeI). Trimethylselenonium is a major excretory product of selenite metabolism. The cytotoxicity of sodium selenite was 1000-fold greater than that of TMSeI. The cytotoxicity of DMA was about the same as that of TMSeI. The mitotic index for DMA administration was increased by these selenium compounds at low concentrations and decreased by them at high concentrations. The tetraploid index for DMA decreased with increasing concentrations of these selenium compounds. Tetraploidy is a form of aneuploidy, and aneuploidy is known to induce carcinogenesis. The finding that selenium inhibited induction of tetraploidy by DMA may yield clues to the role of selenium in the chemoprevention of carcinogenesis by chemical carcinogens.

The toxic effects of arsenic compounds on cell divisionwere studied, using Chinese hamster V79 cells. Seven arsenic compounds weretested. Inorganic arsenic compounds (arsenite and arsenate), which have beenfound in drinking water, inhibited cell growth at very low concentrations. Monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsineoxide (TMAO), which are methylated metabolites of inorganic arsenics, wereless cytotoxic than the inorganic arsenics themselves. The cytotoxicity ofthe three methylated metabolites decreased as the number of methyl groupsincreased. Arsenobetaine (AsBe) and arsenocholine (AsC), which have beenfound in some marine products, did not show any cytotoxicity. Threemethylated metabolites; MMA, DMA and TMAO induced mitotic arrest. Tetraploidyproduction was observed in cells exposed to DMA or TMAO. Arsenite, arsenate,AsBe and AsC did not induce mitotic arrest or tetraploids. These resultssuggest that MMA, DMA and TMAO exert some effect on cell division inmetaphase and may thereby give some clue as to the carcinogenic mechanism ofarsenic.

Arsenicals are epidemiologically significant chemicals in relation to induction of urinary bladder cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMA), a major metabolite of inorganic arsenicals in mammals, for rat urinary bladder carcinogenesis. In experiment 1, 6-week-old male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then given one of several concentrations of DMA in their drinking water (groups 1-6: 0, 2, 10, 25, 50 and 100 p.p.m.) for 32 weeks. The development of preneoplastic lesions and tumors (papillomas and carcinomas) in the urinary bladder was enhanced by treatment with DMA in a dose-dependent manner. A significant increase in multiplicity of tumors (papillomas and carcinomas) was observed even at a low concentration of DMA (10 p.p.m.). On the other hand, no preneoplastic lesions and tumors were observed in the rats treated with DMA alone. In experiment 2, different concentrations of DMA (groups 1-4: 0, 10, 25 and 100 p.p.m.) in drinking water were administered to the rats for 8 weeks without prior initiation by BBN. A significant increase in the 5-bromo-2'-deoxyuridine labeling index and alteration of the surfaces of the urinary bladder epithelial cells, as revealed by scanning electron microscopy, provided evidence of a dose-dependent increase in cell proliferation due to the DMA treatment. These results suggest that DMA has the potential to promote rat urinary bladder carcinogenesis and one of the mechanisms involved is its stimulation of cell proliferation in the urinary bladder epithelium.

A 54-year-old female presented with a rare uterine leiomyosarcoma metastasis to the skull appearing as a gross mass beneath her scalp. She had no neurological or other physical symptoms on admission. Computed tomography and magnetic resonance imaging demonstrated an enhanced dumbbell-shaped mass at the mid-frontal region beneath the scalp. The tumor was totally removed with normal surrounding bone and dura. The histological diagnosis was leiomyosarcoma. Her postoperative course was uneventful, and she received adjuvant chemotherapy. However, multiple distant bone metastases developed 1 year later. Immediate and radical resection of such tumors is recommended.

Operation of esophageal cancer accompanies a big surgical stress and postoperative pulmonary complications such as respiratory failure are observed at high frequencies. On the other hand, when a big stress is added to a body, a state of hypercoagulation in which blood coagulation mechanism is abnormally enhanced appears and this state is closely related to organ failures but has many unknown points. So, we examined 39 patients given excision of esophageal cancer with respect to occurrence of postoperative respiratory failures, participation of coagulopathy in aggravation and their degrees before and after the operation to find out the relationship between postoperative respiratory failure and the state of hypercoagulation. We gave a diagnosis of respiratory failure to the patients whose respiratory index exceeded 1.5 on the day after operation but did not show atelectasis or hydrothorax. As a result, respiratory failures were observed in 7 out of 39 cases (17.9%). When a risk score (RS) of postoperative respiratory failure was determined using multivalent analysis (quantification type II) with preoperative factors such as age and function of heart, lung, liver, and kidney as well as preoperative blood coagulation factors, RS = 2.87 (antithrombin-III (AT-III) less than 75%) +1.89 (age over 70 years) +1.78 (respiratory index over 0.15) +1.44 (serum albumin less than 3.0 mg/dl) +1.28 (cardiac index less than 3.0 l/min/m2) was obtained and a drop in preoperative AT-III was considered a risk for occurrence of post operative respiratory failure. In contrast, referring changes in postoperative value of blood coagulation factors, a distinct rise in fibrinogen (FBG) appeared in early stage after operation in the respiratory failure group compared to the control group (p < 0.01). Moreover, recovery in AT-III of blood coagulation factors and in plasminogen and antiplasmin of fibrinolytic factors was delayed (p < 0.05) indicating promotion of postoperative hypercoagulation state and delay in recovery of coagulation-fibrinolysis factors. However, participation of platelet factors was absent.

The CadC protein from the cadA cadmium resistance operon of Staphylococcus aureus plasmid pI258 regulates transcription of this system in vitro. The CadC protein was overproduced in Escherichia coli cells and partially purified. Gel shift assays of the proposed cadA operator/promoter region DNA showed specific association with the CadC protein. Control arsenic resistance operator/promoter DNA from the same plasmid was not shifted by the CadC protein. Cd2+, Bi3+, and Pb2+ caused the release of CadC from DNA in gel retardation assays. DNase I footprinting measurements showed that the CadC protein specifically associated with and protected a region of operator/promoter DNA from nucleotide positions -7 to +14 relative to the start point of mRNA synthesis. Runoff transcription assays with the operator/promoter region of DNA (plus the first 69 nucleotides of the cadC gene) and purified E. coli RNA polymerase gave an mRNA product of the predicted size. Added CadC protein inhibited transcription in vitro.

Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N-nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form-positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans.

We improved the method for determining urinary delta-aminolevulinic acid (ALA) by HPLC-fluorometer after pre-column derivatization with acetylacetone and formaldehyde, and a stable ALA derivative was obtained without any effect from various urinary components as demonstrated by the complete recovery of ALA (100.9 +/- 5.5%, n = 85) from the urine samples. The modified procedure was as follows: Twenty microliters of urine sample, 5 ml of acetylacetone solution (acetylacetone/ethanol/distilled water containing 4 milligrams of NaCl; 15/10/75), and 0.45 ml of 9.3% formaldehyde solution were mixed and boiled for 15 min. The fluorescent derivative of ALA was separated and analyzed by HPLC with the fluorometer at Ex 246 nm and Em 458 nm. Using a gradient program, the retention time of the ALA derivative was 7.3 min and the analysis could be repeated at 13 min intervals. Concentrations of ALA in urine samples measured by this method were significantly correlated with those measured by the Mauzerall-Granick (M-G) method (n = 85, r = 0.993, p < 0.001). The values obtained by our method were, however, lower than those obtained by the M-G method. Urinary ALA concentrations of 40 non-lead workers ranged from 0.1 to 2.3 mg/g creatinine with the mean +/- SD of 1.1 +/- 0.4 mg/g creatinine as measured by the present method.

Urinary alpha 1-microglobulin (alpha 1-m) and beta 2-microglobulin (beta 2-m) can be used as early indicators of renal tubular dysfunction. However, low levels of lead exposure cause an increase in urinary alpha 1-m, but not in urinary beta 2-m. In order to clarify the level of tubular dysfunction in early lead nephropathy, fractional clearances of alpha 1-m (FC-alpha 1-m) and beta 2-m (FC-beta 2-m), i.e., the ratios of these clearances to the creatinine clearance, were measured in 99 male lead workers. Blood urea nitrogen, serum creatinine, uric acid, and urinary creatinine and N-acetyl-beta-D-glucosaminidase activity were also measured to diagnose the presence of other renal dysfunction. The median of FC-alpha 1-m was 0.13% in the control group. The FC-alpha 1-m increased in lead workers with blood lead (B-Pb) levels above 20 micrograms/dl. The correlation of FC-alpha 1-m with urinary alpha 1-m was highly significant, but there was no correlation with serum alpha 1-m. The median of FC-beta 2-m was 0.065% in the control group. There was a correlation of FC-beta 2-m with FC-alpha 1-m, but there was no correlation with B-Pb, or with serum beta 2-m. These results suggest the following: There was a very low excretion rate of alpha 1-m and beta 2-m in both the control group and the lead exposed groups. The excretion rate of alpha 1-m was higher than that of beta 2-m.(ABSTRACT TRUNCATED AT 250 WORDS)

The nephrotoxicity of dimethylarsinic acid (cacodylic acid, DMA) was examined in male and female F344/DuCrj rats. DMA administered perorally at doses of 113, 85, and 57 mg/kg for 4 weeks produced dose-related decreases in body weight and survival rate in both sexes. Mortality was higher and appeared more quickly in females than in males. Histopathological findings in the kidney were proximal tubular degeneration and necrosis, as well as papillary necrosis, and hyperplasia of the epithelium covering the papillae. Since extensive proximal tubular necrosis was observed only in dead animals of both sexes, and not in survivors or the controls, it was therefore concluded that the main cause of death could be attributed to nephrotoxicity of DMA. The results thus show that DMA is nephrotoxic to both male and female rats.

Serum immunoglobulin and complement C3 levels were measured in workers exposed to lead at a secondary lead refinery and a solder factory. In the first survey, significant correlations were found between blood lead and IgA with a correlation coefficient of 0.296, and between blood lead and IgE with a correlation coefficient of 0.314. No other significant correlations were found among the indicators of lead exposure and humoral immunity. In the second survey, no significant correlations were found between blood lead and IgG and IgA. A significantly higher number of subjects with IgE of more than 400 IU/ml was found in the group with blood lead of more than 60 micrograms/100 g.

Genotoxicity of 10 pesticides (chlornitrofen, chlomethoxyfen, molinate, thiobencarb, simazine, simetryn, diazinon, iprofenfos, piperofos and oxadiazone) was studied by mitotic toxicity, sister chromatid exchange, and rec assay. The pesticides are detected frequently at high levels in the Yodo River water in Osaka, Japan, which is used for drinking water by thirteen million people. Mitotic toxicity was evaluated by mitotic index (MI) and second mitosis index (SI), using a Chinese hamster cell line V79. SI is the rate of twice divided metaphases in chromosome preparation for sister chromatid exchange. All the pesticides decreased the two indices dose-dependently. MI50 and SI50, the concentrations of pesticides which lowered the indices to 50% of the solvent control, was determined. The MI50 and SI50 of each pesticide were very similar, and the pesticides did not hinder cell division specifically. None of the pesticides induced more sister chromatid exchanges than 1.5 times the solvent control. Chlomethoxyfen and simazine induced sister chromatid exchanges significantly in V79 cells, but the dose dependencies were poor. Simetryn had rec effect and was concluded to have DNA damaging activity.

Three thermophilic Methanothrix ("Methanosaeta") strains, strains PTT (= DSM 6194T) (T = type strain), CALS-1 (= DSM 3870), and Z-517 (= DSM 4774), were characterized chemotaxonomically and compared with five mesophilic strains, Methanothrix soehngenii ("Methanosaeta concilii") GP6 (= DSM 3671), Opfikon (= DSM 2139), FE (= DSM 3013), UA, and PM. These methanogens were exclusively acetotrophic and had a characteristic sheathed structure. The DNA base compositions of the strains which we studied ranged from 50.3 to 54.3 mol% guanine plus cytosine. The thermophilic strains often had phase-refractive gas vesicles inside their cells. Denaturing electrophoresis of proteins showed that the mesophilic and thermophilic Methanothrix strains formed two distinct groups and that there were differences in protein patterns between the groups. The difference between the thermophiles and mesophiles was also verified by comparing partial 16S rRNA sequences (ca. 30 base differences in ca. 540 bases). On the basis of our results, we propose the name Methanothrix thermophila for the three thermophilic strains. The type strain of M. thermophila is strain PT (= DSM 6194). We also propose that the name Methanothrix thermoacetophila ("Methanosaeta thermoacetophila"), which was given to strain Z-517 (type strain), should be rejected because of its description, which was based on an enrichment culture, was inadequate.

The genotoxicity of beryllium, gallium and antimony compounds was studied with the rec, Salmonella mutagenicity and SCE assays. In the rec assay, all the salts of the metals, BeCl2, Be(NO3)2, GaCl3, Ga(NO3)3, SbCl3, SbCl5, and an oxide, Sb2O3, had DNA-damaging activity. None of the compounds was mutagenic to Salmonella. In the SCE assays using V79 cells, 2 antimony(III) compounds, SbCl3 and Sb2O3, and 2 beryllium compounds, BeCl2 and Be(NO3)2, induced SCEs significantly. Sb2O3, slightly soluble in water, was positive in both the rec assay and the SCE assay at very low doses.

Erythrocyte deformability and other hematological indicators were determined in 17 male workers exposed to lead at a secondary lead refinery and 13 controls. Blood lead, urine lead, urine coproporphyrin, delta-aminolevulinic acid and erythrocyte zinc protoporphyrin were determined to evaluate the degree of lead exposure in the lead workers above. For the measurement of erythrocyte deformability, the microfilter method was used. The results were summarized as follows: 1. The mean values of blood lead, urine lead, urine coproporphyrin, urine delta-aminolevulinic acid and erythrocyte zinc protoporphyrin levels in lead workers were 53.5 micrograms/100g, 141.4 micrograms/l, 115.9 micrograms/l, 12.0 mg/l and 68.9 micrograms/dl respectively, suggesting a moderate influence of lead exposure. 2. The mean values of erythrocyte count, hematocrit and hemoglobin were significantly lower in lead workers than those in controls. No significant differences were found in the mean values of mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and corpuscular natrium and potassium between lead workers and controls. 3. Erythrocyte deformability was significantly reduced in lead workers compared with controls.

The mutagenicity of 1-nitropyrene was strongly enhanced in the Salmonella mutagenicity test with the preincubation modification when it was dissolved in dimethylsulfoxide and diluted with water. The enhancement of mutagenicity was not found in the plate incorporation method and seemed to be common to chemicals which have low solubilities in water. The indications were that the effectiveness of preincubation modification was due to the increased absorption of test chemicals by the Salmonella cells, and that the absorption depends primarily on the solubility of test chemicals in the assay mixture.

A case of lead poisoning in a secondary lead refinery was reported. A 58 year old man working at the post of lead refining complained of severe lassitude and diarrhea. By increased urine coproporphyrin excretion, he was suspected of a case of lead poisoning. Clinical data from the health examinations revealed that he had been affected by lead. The patient was transposed to another work post where lead was not handled and rapidly recovered from the poisoning.

The adverse effects of long-term exposure to lead dust on renal tubular functions were studied in 39 male and 7 female workers in a secondary lead refinery. Laboratory examinations showed low or moderate lead absorption levels. The N-acetyl-beta-D-glucosaminidase (NAG) activity in urine showed significant correlation with each of the lead exposure indices. NAG activity increased remarkably in lead workers with blood lead (PbB) above 80 micrograms 100g-1. Blood urea nitrogen (BUN) showed significant correlation with PbB and logarithmic urine delta-amino-levulinic acid (log(ALAU)), but not with urine lead (PbU) and logarithmic urine coproporphyrin (log(CPU)). All the other indices of renal function were almost within the normal range and showed no correlation with lead indices. This study suggests that moderate lead absorption may cause renal tubular impairment, and NAG can be one of the most sensitive indices for estimating renal dysfunction due to lead poisoning.

Cancer mortality was studied among 265 male workers in 40 small plating factories (chromium, copper and nickel) where bicycle parts are plated. The study utilized record linkage with the Osaka Cancer Registry file between January 1, 1965 and December 31, 1979. The results showed that seven workers had died of cancer, and the Standardized Mortality Ratio (SMR) calculated for all cancers, stomach cancer and lung cancer were 1.13, 1.23 and 1.11, respectively, with no significant relationship found between the observed and expected values. The SMR for lung cancer among those workers with a high degree of skin ulceration and with perforation of the nasal septum was high, 11.22 and 5.13, respectively, although not statistically significant because of the small sample size in the study. The results suggest that lung cancer occurs in those subjected to a high degree of exposure to chromium.

The characteristics of the degradation of cellulose, soluble starch, and glucose in the acidogenic phase and the effects of the substrate loading rate and biological solids retention time on the methanogenic phase of anaerobic digestion were investigated. The results obtained from continuous experiments using laboratory-scale anaerobic chemostat reactors elucidated the true rate-limiting step of anaerobic digestion. The specific rate of substrate utilization decreased in the following order: glucose, soluble starch, acetic acid, and cellulose. The rate of the hydrolysis of cellulose was so low that this was shown to be the rate-limiting step in overall anaerobic digestion. Among methanogenic bacteria Methanosarcina would provide a higher substrate utilization rate than Methanothrix, and the maximum allowable substrate loading rate in the methanogenic phase was 11.2 g acetic acid/L day.

Cadmium induced renal tubular effects were examined in 65 female workers in a factory manufacturing nickel cadmium batteries. Urinary beta 2-microglobulin (beta 2m), urinary N-acetyl-D-glucosaminidase activity (NAG), and serum creatinine and serum urea concentrations were used to assess the renal effects. Of the four measures, only urinary NAG and urinary beta 2m showed a strong positive correlation with blood cadmium concentrations (r = 0.49 and 0.43 respectively); NAG showed a weaker correlation with urinary cadmium concentrations (r = 0.35). Urinary beta 2m has weak correlation with urinary cadmium (r = 0.04). Only urinary NAG showed a significant deterioration in renal function among the exposed group. NAG detects the largest proportion of abnormalities among the exposed group. Abnormal urinary beta 2m is detected in only 15.4% of the workers, half of whom have blood cadmium above 10 micrograms/l. The proportion of abnormalities detected by urinary NAG differs significantly from the proportion of abnormalities detected by urinary beta 2m (p less than 0.01). The age adjusted mean urinary NAG excretion showed a significant rise with urinary cadmium of above 3 micrograms/g creatinine. Urinary beta 2m failed to show any significant rise. With blood cadmium concentrations, the age adjusted mean urinary NAG excretion showed a rise from 1 microgram/l of blood cadmium followed by a plateau between blood cadmium concentrations of 3-10 micrograms/l. No significant rise in mean urinary excretion in beta 2m was seen until blood cadmium concentrations exceeded 10 micrograms/l.