Koichi Haraguchi

Mercury and selenium concentrations in the internal organs of toothed whales and dolphins marketed for human consumption in Japan

Small cetaceans (toothed whales odontoceti and dolphins delphinidae) have been traditionally hunted along the coast of Japan and fresh red meat and blubber, as well as boiled internal organs such as liver, kidney, lung and small intestine, are still being sold for human consumption. We surveyed mercury contamination in boiled liver, kidney and lung products marketed in Japan between 1999-2001. The average +/- S.D. of total mercury (T-Hg) was 370 +/- 525 (range: 7.60 approximately 1980, n = 26) microg/g in liver, 40.5 +/- 48.5 (7.30-95.1, n = 15) microg/g in kidney and 42.8 +/- 43.8 (2.10-79.6, n = 23) microg/g in lung. A high correlation was observed between T-Hg and selenium (Se) concentrations in these organs, supporting the formation of a Hg-Se complex. The formation of a Hg-Se complex probably contribute to the detoxification of Hg for cetaceans and allows a very large accumulation of Hg in livers. The provisional permitted level of T-Hg in marine foods set by the Japanese Ministry of Health and Welfare is 0.4 microg/ g, and the provisional permitted weekly intake (PTWI) set by WHO is 5 microg/kg bw/week. The maximal T-Hg detected in boiled liver (1,980 microg/g) exceeds the permitted level by approximately 5,000 times and the consumption of only 0.15 g of liver exceeds the PTWI of 60 kg of body weight of the consumer, suggesting the possibility of an acute intoxication by T-Hg even after a single consumption of the product.

Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats

Abstract Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO2) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO2-2,2′,3′,4′,5,6-hexachlorobiphenyl (3-MeSO2-CB132); 3-MeSO2-2,2′,3′,4′, 5,5′-hexachlorobiphenyl (3-MeSO2-CB141); 3-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (3-MeSO2-CB149) and 4-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (4-MeSO2-CB149). The congeners were major MeSO2-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO2 metabolites (20 μmol/kg once daily for 4 days) reduced serum total thyroxine levels by 22–44% at a much lower dose than phenobarbital (PB; 431 μmol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO2-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO2-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO2-CB132, 3-MeSO2-CB141 and 3-MeSO2-CB149, but not by 4-MeSO2-CB149. Thus, it is likely that the 3-MeSO2-hexachlorobiphenyls and 4-MeSO2-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO2 metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters.

Inhibition of cell-cell communication by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rat liver epithelial IAR 20 cells

The effects of three polychlorinated biphenyl (PCB) congeners and their six methylsulfonyl (MeSO2)-metabolites on cell communication have been investigated in the scrape-loading/dye-transfer assay in IAR 20 rat liver epithelial cells. The results demonstrated that at non-cytotoxic concentrations 2,2′,4′,5-tetrachlorobiphenyl, 2,2′,4′,5,5′-pentachlorobiphenyl (2,2′,4′,5,5′-pentaCB), 2,2′,4′,5,5′,6-hexachlorobiphenyl (2,2′,4′,5,5′, 6-hexaCB), and their 3- and 4-MeSO2 derivatives completely inhibited the cell communication within 1 h. 4-MeSO2-2,2′,4′,5,5′-pentaCB and 4-MeSO2-2,2′,4′,5, 5′,6-hexaCB appeared to inhibit the cell communication at slightly lower concentration than their parental PCB congeners and 3-MeSO2 derivatives. The results show that 3- and 4-MeSO2 derivatives of the PCB congeners tested inhibit gap junction intercellular communication at about the same potency as their parental compounds. Since inhibition of cell communication is often observed after treatment with many tumor promoters, our findings suggest that the metabolites may also act as tumor promoters.