Noburu Ishinishi

Arsenic intake and excretion by Japanese adults: A 7-day duplicate diet study

The amount of arsenic in the urine, faeces and in duplicate diets of two couples who had eaten customary Japanese meals were monitored for 7 days by arsine-generator atomic absorption spectrophotometry. For the four volunteers, the mean daily intake of arsenic from their diets was 182 micrograms (range 27 to 376 micrograms). The dietary arsenic was composed of 5.7% inorganic arsenic, 3.6% methylarsonic acid, 27.4% dimethylarsinic acid and 47.9% trimethylarsenic compounds. The mean amounts of arsenic eliminated daily in urine and faeces were 148 micrograms (50-416 micrograms) and 46 micrograms (0-138 micrograms), respectively. The urinary arsenic was composed of 1.4% inorganic arsenic, 3.5% methylarsonic acid, 33.6% dimethylarsinic acid and 61.4% trimethylarsenic compounds. The daily intake of arsenic influenced the total amount of arsenic excreted in the urine (r = 0.7302, P less than 0.01) and the amount eliminated in the faeces (r = 0.5900, P less than 0.01) the next day. Specifically, there was also a significant correlation between the daily intakes of trimethylarsenic compounds and dimethylarsinic acid and the amounts of these compounds found in the urine the following day (r = 0.6833, P less than 0.01 and r = 0.6630, P less than 0.01, respectively). Considering the amounts of arsenic compounds present in seafood and in other components of the diet together with the urinary elimination patterns of arsenic compounds, it seemed probable that the trimethylarsenic compounds in the urine originated largely from fish and shellfish, which contain mainly arsenobetaine. Trimethylarsenic compounds in the urine should therefore be the preferred indicator of arsenic arising from the ingestion of seafood, especially fish and shellfish. In this study, the mean daily intake of inorganic arsenic from the diet (0.18 micrograms/kg) did not exceed the FAO/WHO JECFA Tolerable Daily Intake of 2 micrograms inorganic arsenic kg.

Tumorigenicity of arsenic trioxide to the lung in Syrian golden hamsters by intermittent instillations

The tumorigenicity of arsenic trioxide was investigated in female Syrian golden hamsters which were given a total of 5.25 mg or 3.75 mg as arsenic by intratracheal instillations once a week. As controls, hamsters were treated with the vehicle, phosphate buffer solution. During the total life span, 3 lung adenomas were manifested in 10 hamsters or 2 lung adenomas in another 20 hamsters after 15 instillations of arsenic, while no lung tumor was detected among 35 hamsters in 2 control groups. The results show that arsenic trioxide is tumorigenic to the lung of Syrian golden hamsters.

Effects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters

Our previous study showed that pretreatment with buthionine sulfoximine (BSO), which inhibits glutathione synthesis, results in acute renal failure with oliguria in hamsters ingesting sodium arsenite (5 mg As/kg). For a deeper understanding of the relationship between arsenic metabolism and the subsequent development of nephrotoxicity, we studied excretion, tissue retention, biotransformation, pharmacokinetics, and histopathological events in the kidneys of hamsters both with and without BSO pretreatment. The total amount of arsenic excreted in the urine and feces within 72 hr of arsenite administration was more than fivefold lower in BSO-pretreated animals than in the controls without pretreatment (9.2 versus 53.4% of the arsenic dose). The persistence of high amounts of total arsenic was apparent in the blood, liver, and kidneys of BSO-pretreated hamsters, even though the content of inorganic arsenic steadily decreased with time. The disappearance of inorganic arsenic from the blood showed a biphasic elimination pattern characterized first by a rapid component with a half-life of 4.5 hr and second by a slower component with a half-life of 58.0 hr in the BSO-pretreated hamsters, while these half-lives were 0.6 and 11.0 hr, respectively, in the controls. BSO pretreatment not only impaired the excretion of inorganic arsenic, but also impaired its methylation. Combined BSO/arsenite treatment resulted in renal tubular necrosis which was prominent at 1 hr after arsenite administration. By 1 hr, the renal content of inorganic arsenic in the BSO-pretreated animals was 1.7 times higher than that in the controls. This study demonstrates that glutathione depletion elicits the nephrotoxic manifestations of arsenic poisoning.

Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters

The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters.

Mutagenic activity of the leachate of municipal solid waste landfill

Organic concentrates were recovered using XAD-2/8 resin adsorption from the leachates of municipal solid waste landfills and their mutagenic activities were tested for 8 months using the Ames Salmonella/microsome assay. Highly polluted leachates (COD and BOD > or = 40 mg/l) generally had equal or higher mutagenic activities than lightly polluted leachates (COD and BOD < 40 mg/l). But there was no clear difference in mutagenicity per amount of concentrate between the two leachates. These results suggest that the mutagenic activity of landfill leachate is decided to some degree by the organic concentration in the leachate. The mutagenic activities detected even in lightly polluted leachates were not so low as those of various kind of surface waters ever reported. It is suggested that it is important to investigate the mutagenic activity of the leachate for evaluation of the impact of landfill leachate on the environment.

Lead levels in ancient and contemporary Japanese bones

During the past few centuries, lead production, consumption and emissions, to our total environment have increased remarkably. We have determined the concentrations of lead in 41 well-preserved ancient and 11 contemporary rib bones of a mature age (40–60 y), with a view to historically evaluating lead exposure in humans. The oldest Japanese bones (1000–300b.c.) were found to contain a mean of 0.58 μg Pb/g dry wt and a mean molar ratio of lead to calcium of 0.6×10−6, compared with 4.7–5.2×10−6 in the bones of the Edo era (1600–1867a.d.) and contemporary residents in Japan. The mean molar ratios of female bones were always higher than those of male bones for each era. From this fact we may assume that facial cosmetics were one of the main routes of lead exposure among the ancient Japanese, especially those who lived during the Edo era.

Variation of trace metals in ancient and contemporary Japanese bones

Excavated and contemporary bones (rib cortexes) of a mature age (40–60 yr) were analyzed by atomic absorption spectrometry for the concentration of seven elements, including Ca, Cd, Cu, Fe, Mn, Ni, and Pb, with a view to historically evaluating the chemical composition of the bones. Fifty-two well-preserved specimens, obtained from western Japan, were classified into six groups according to Japanese prehistoric and historic eras (Jomon, Yayoi, Kofun, Muromachi, Edo, and Contemporary). Average concentrations of Ca were 0.20–0.33 g/g in the excavated bones and 0.17 g/g in the contemporary bones. Among the trace metals, such as Cu, Fe, Mn, and Pb, which showed remarkably elevated concentrations in the Edo era bones, Cu, Fe, and Mn were found to be strongly associated with soil contamination. Lead levels only slightly increased between the Jomon and Kofun eras, but became abruptly elevated following the Edo era. In contrast, the concentrations of Cd increased abruptly in the Yayoi era to a level with an order of magnitude higher than the Edo era, and they have recently decreased to rather low contemporary levels. This tendency becomes clearer when comparing the molar ratio of trace metals to Ca. The cause of elevated Cd concentrations in early excavated bones is discussed in relation to the mineralization of bones and the surrounding environment.

Recovery from changes in the blood and nasal cavity and/or lungs of rats caused by exposure to methanol-fueled engine exhaust

One group of male, pathogen-free, Fischer 344 rats was exposed to about 17-fold diluted exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h, and then the rates of recovery from the resulting increased levels of plasma formaldehyde and carboxyhemoglobin in their erythrocytes were measured. The carboxyhemoglobin level in the erythrocytes was restored within 4 h, whereas the plasma formaldehyde level was still elevated after 4 h but was restored to the normal level within 8 h. No methanol or formic acid was detected in the plasma. Another group of rats was exposed to the same dilution of exhaust for 8 h/d for 7 d, and then the recovery from histopathological damage of the nasal cavity and lungs was also examined. Hyperplasia/squamous metaplasia and erosion of the respiratory epithelium lining the nasoturbinate, maxilloturbinate, or nasal septum, and infiltration of neutrophils into the submucosa at level 1 (level of the posterior edge of the upper incisor teeth) were observed immediately after the exposure period. Lesions of the respiratory epithelium at level 2 (incisive papilla) were less than those at level 1. Slight lesions at levels 1 or 2 were still noticed 1 wk after exposure, but not 4 wk after exposure. Just after exposure, decreases of Clara cells in the terminal bronchiolus and of cilia in the bronchial/bronchiolar epithelium were also observed. Moreover, focal hypertrophy of alveolar walls and increase of macrophages were observed in parts adjacent to respiratory bronchiolus. One week after the exposure period, these changes were no longer seen. These results indicate that changes in the blood and in the nasal cavity and lungs caused by methanol-fueled engine exhaust are reversible. However, complete recovery from damage of the nasal cavity caused by 7-d exposure to the exhaust takes 4 wk, and recovery from elevated plasma formaldehyde and erythrocyte carboxyhemoglobin levels caused by a single 8-h exposure takes 4-8 h.

Toxicity to rats of methanol‐fueled engine exhaust inhaled continuously for 28 days

Fischer 344 rats were exposed to three concentrations of exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h/d, 7 d/wk for 7, 14, 21, or 28 d. Concentration- and time-dependent yellowing of the fur was prominent in all treated groups. Concentration-dependent increases in the erythrocyte count, hematocrit, hemoglobin concentration, formaldehyde in plasma, and carboxyhemoglobin in the erythrocytes, and decrease in serum alkaline phosphatase activity were seen after all exposure periods. Histopathologically, lesions were found in the nasal cavity and lungs after 7 d of exposure. Squamous metaplasia of the respiratory epithelium of level 1 (level of the posterior edge of the upper incisor teeth) lining of the nasoturbinate and/or maxilloturbinate and infiltration of neutrophils into the submucosa, and decreases of Clara cells in the terminal bronchiolus and of cilia in the bronchiolar epithelium, were observed in the high-concentration group (carbon monoxide, 94 ppm; formaldehyde, 6.9 ppm; methanol, 17.9 ppm; nitrogen oxides, 52.7 ppm; nitrogen dioxide, 10.6 ppm). The histopathological extents of several lesions increased slightly with the exposure time. Slight squamous metaplasia and hyperplasia of the respiratory epithelium at level 1 were also observed in the medium-concentration group (one in three of the high-concentration group). No histopathological changes were found in the olfactory epithelium of the nasal cavity. In the low-concentration group (one in nine of the high-concentration group), no marked histopathological changes in these organs were observed. These results may suggest that the lesions observed in the nasal cavity of rats exposed to methanol-fueled engine exhaust were mainly caused by formaldehyde, although other components in the exhaust also may have affected nasal cavity and/or lungs to less extent.

Ingestion of parsley inhibits the mutagenicity of male human urine following consumption of fried salmon

The urinary mutagenicity of 3 nonsmoking, healthy men was investigated after strictly defined meals by means of the Ames Salmonella/microsome test. When the subjects ate 150 g of fried salmon at one meal, a potent mutagenicity of almost 5000 revertants of TA98 strain was present in all 6-h urine samples. On the other hand, less than 2500 revertants was present in the urine when the subjects simultaneously consumed 70 g of parsley and 150 g of fried salmon. Thus, the protection against mutagenicity affected by parsley warrants further attention.