Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber syndrome) is an autosomal dominant disorder characterized by aberrant vascular development. We report here a genetic epidemiologic study in a county, A, in the Akita prefecture (population 1.2 million) located in northern Japan. Nine HHT patients who had been referred to tertiary-care hospitals were located in and near the study county. A total of 137 pedigree members were traced of which 81 were alive and 32 were affected by HHT. Complications associated with cerebral or pulmonary arteriovenous malformations were proven in six out of seven families. Linkage analysis in two large families revealed a weak yet suggestive linkage to the HHT1 locus (encoding endoglin; ENG). Three novel mutations were found in four families, all of which led to a frameshift: a G to C transversion at the splicing donor site of intron 3 (Inv3+1 G>C) in one family, one base pair insertion (A) at nucleotide 828 (exon 7) of the endoglin cDNA in two large families (c.828-829 ins A), and a four base pair deletion (AAAG) beginning with nucleotide 1120 (exon 8) of the endoglin cDNA (c.1120-1123 delAAAG) in one family. The insertion of A in exon 11 (c.1470-1471 insA) mutation found in one family has also been reported in a European family. No endoglin gene mutations were found in two families. The population prevalence of HHT in the county was estimated to be 1:8,000 approximately 1:5,000, roughly comparable with those reported in European and U.S. populations, which is contradictory to the traditional view that HHT is rare among Asians. We recommend that families with HHT be screened for gene mutations in order that high-risk individuals receive early diagnosis and treatment initiation that will substantially alter their clinical course and prognosis.

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Arsenic toxicity is a global health problem affecting many millions of people. The main source of exposure is drinking water contaminated by natural geological sources. Current risk assessment is based on the recognized carcinogenicity of arsenic, but neurotoxic risks have been overlooked. In 1955, an outbreak of arsenic poisoning occurred among Japanese infants, with more than 100 deaths. The source was contaminated milk powder produced by the Morinaga company. Detailed accounts of the Morinaga dried milk poisoning were published in Japanese only, and an overview of this poisoning incident and its long-term consequences is therefore presented. From analyses available, the arsenic concentration in milk made from the Morinaga milk powder is calculated to be about 4-7 mg/L, corresponding to daily doses slightly above 500 μg/kg body weight. Lower exposures would result from using diluted milk. Clinical poisoning cases occurred after a few weeks of exposure, with a total dose of about 60 mg. This experience provides clear-cut evidence for hazard assessment of the developmental neurotoxicity. At the present time, more than 600 surviving victims, now in their 50s, have been reported to suffer from severe sequelae, such as mental retardation, neurological diseases, and other disabilities. Along with more recent epidemiological studies of children with environmental arsenic exposures, the data amply demonstrate the need to consider neurotoxicity as a key concern in risk assessment of inorganic arsenic exposure.

µg/dl for industrial workers and 5 µg/dl for children. To examine whether the critical level of lead producing adverse effects truly differs between workers and children, we provided an overview of studies addressing the critical level of lead in workers, together with a perspective on lead toxicity in children. Data sources and extraction: In 25 reports published in English with keywords of "benchmark dose (BMD)," "lead" and "humans," only five studies proved to be relevant to lead toxicity. Four more studies with figures illustrating significant relationships between lead and neurotoxic outcomes were selected. Data synthesis: Based on data from previous reports using a BMD approach, the critical organ of lead in workers was thought to be the nervous system and the critical BPb level (numberweighted mean) was between 10.7 and 17.5 µg/dl. The neurotoxic effects of lead exposure at such levels seemed reversible. The BPb level at which leadassociated intellectual deficits occurred in children was as low as the critical level of BPb (below 5 µg/dl) for inhibited heme synthesis in workers. Conclusions: The neurotoxic effects of lead in workers appear to be initiated at BPb levels below 18 µg/dl, which are somewhat higher than the critical level of lead neurotoxicity in children. Each national institute for risk Review management should take evidence-based preventive action against subclinical lead poisoning in workers, as well as in children. (J Occup Health 2009; 51: 1-12)

It is suggested that Japanese children may ingest similar doses per body weight of methylmercury to their mothers. If maternal hair mercury was used as a proxy for mercury exposure at birth, no significant dose-effect associations with the BAEP latencies were observed in Japanese children with exposure levels below 6.9 mug/g of hair mercury, but only when higher-level exposures from Madeiran children were included. The BMDL was lower for the merged data than for Madeiran children alone.