Akira Hisanaga

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.

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.

A comparison of the carcinogenicity of N-nitrosodiethylamine and N-nitrosodimethylamine after intratracheal instillation into Syrian golden hamsters

N-Nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) were instilled intratracheally into male Syrian golden hamsters once a week for 15 wk. The total dosages were 1.5 mg and 7.5 mg of NDEA and 0.75 mg and 1.5 mg of NDMA. A control group simultaneously received phosphate buffer vehicle. Tumours related to instillation appeared principally in the respiratory tract and the liver. Over the entire lifespan of the animals tumour incidence rates in the respiratory tract were 100% in both the NDEA groups, 6% in both NDMA groups and 8% in the control group. The total incidences of liver tumours were 6% in the 0.75 mg NDMA group, 19% in the 1.5 mg NDMA group, zero in the NDEA groups, and 4% in the control group. These results indicate that, when administered by this route, NDEA is a much more potent carcinogen in the respiratory tract than is NDMA but NDMA alone seems to be carcinogenic to the liver, at a total dosage of 1.5 mg.