Several reports on the decreasing quantity of sperm production in human over the last four decades and on the increased incidence of certain cancers and endometriosis have increased concern about environmental chemicals, i.e., drugs, agricultural and industrial chemicals, and dioxins that can disrupt the endocrine system, although no link has been established between an endocrine-based disease and exposure to an environmental chemicals. Therefore, there is accumulating evidence that wild animals have suffered adverse reproductive consequences from exposure to environmental chemicals and a wide variety of environmental chemicals has been identified to have ability to interact with the endocrine system. Moreover, it is well recognized that the normal functions of all organ systems are regulated by endocrine factors, and small disturbances in the endocrine function, especially during certain stages of the life cycle such as development, pregnancy, and lactation, can lead to profound and lasting effects. Here, I compile representative classes of possible endocrine disruptors, and review the toxicities in animal models and possible mechanisms proposed to explain their effects as endocrine disruptors.

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Mercury exists as elemental mercury (liquid mercury or mercury vapor), inorganic mercury salts (mercurous or mercuric), and organic mercury compounds (aryl- or alkylmercury). Due to the different chemical and physiological properties of all forms of mercury the effects of mercury on humans shows quite different clinical pictures. In this paper, mercury vapor and inorganic mercury poisoning are mainly reviewed. Liquid mercury, since it is poorly absorbed from the gastrointestinal tract, is nontoxic. Mercury vapor (Hg⁰) is absorbed rapidly from the alveolar membrane by inhalation and is accumulated mainly in the brain and kidney. In acute exposure to high concentrations of mercury vapor, the symptoms of respiratory, such as chest pain, cough, hemoptysis, and interstitial pneumonitis occur shortly after inhalation. In chronic exposure to relatively low concentrations of mercury vapor, neurological changes are prominent. The signs and symptoms of mercury vapor poisoning is characterized by gingivitis, intentional tremor and erethism, and in addition, weakness, fatigue, loss of weight, and disturbance of gastrointestinal functions appear unspecifically. Effects of inorganic mercury toxicity manifest in the gastrointestinal tract and kidney after ingestion. Early signs and symptoms appear as pharyngitis, dysphagia, abdominal pain, nausea and vomiting, and bloody diarrhea. Afterward renal failure due to necrosis of the proximal tubular epithelium occurs and develops into anuria and uremia. The occurrences of mercury vapor poisoning due to occupational or accidental exposures and inorganic mercury poisoning due to accidental or suicidal ingestion are reducing today in Japan.

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A simple and highly reliable screening method for unknown toxic substances in biological samples is required to select effective treatments for intoxicated patients in emergency medical care. For toxicological screening, and analytical method for pesticides in human serum by reversed-phase liquid chromatography with photo-diode-array detection was investigated. Twenty six commonly used pesticides could be identified from their UV spectra and retention times. The detection limit was less than 10 ng per injection, which was enough to identify pesticides in serum after solid-phase extraction using an ODS cartridge (Bond Elute C18). We analyzed the sera of three patients with this method and showed that the method was accurate and sensitive enough to identify unknown pesticides. The time needed for analysis was only 2-2.5h. We propose that this method will be very useful for detecting pesticides responsible for poisoning in emergency medical units.

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Senna leaf, senna pod and rhubarb are the strong laxative crude drugs peculiarly containing such effective components as sennoside A (SA) and sennoside B (SB). These crude drugs are prescribed as ingredients used only as drugs by the notification of Pharmaceutical Affairs Bureau. Therefore, foods containing these drugs are regulated as illegal drugs, unapproved/unpermitted drugs, on the Pharmaceutical Affairs Law. We had successfully identified and detected rhubarb besides senna leaf and senna pod from some of imported herbal teas which were regarded as "health foods."The established method for the identification of these drugs is as follows. As the accurate method for the detection of characteristic common components of SA and SB three dimensional-HPLC (3D-HPLC) and TLC were utilized and they were distinguished each other based on the peculiarities shown below. 1. Rhein 8-glucoside is a characteristic component of rhubarb and successfully detected by 3D-HPLC. 2. On the TLC chromatogram for the identification method of senna or rhubarb described in Japanese Pharmacopoeia (JP), each unique spot could be found, a pale white spot at senna, a remarkable orange-yellow spot usually observed on a mixture of free anthraquinones, chrysophanol, emodin, aloeemodin, etc. at rhubarb. 3. Through magnifying glass, even from cut samples, each characteristic tissue is found, namely pieces of leaves with an entire, acuminate, asymmetric leaf base, swelling veins or some hairs on the senna leaf, glossy pieces of pod changed to dark in place and often retuse seeds on senna pod, and brownish porous pieces of rhubarb. 4. Under a microscope, warty hairs from senna leaves and large clustered crystals (over 50μm) with vessels, pigments and other components from rhubarbs could be respectively observed as described in JP.

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Potato starch (PS) was carboxymethylated with monochloroacetic acid to prepare sodium carboxymethyl starches (Na-CMSs) with different degrees of substitution (DS) at the OH moieties, and their first thermal decomposition was invesitigated at 200 to 300°C. Chemical analyses suggested that Na-CMSs (1), (2) and (3) having DS≤0.3 were the compounds substituted with carboxymethyl groups at the primary OH moieties and Na-CMSs (4), (5) and (6) having 0.3≤DS<1.1 at both primary and secondary OH moieties. Remarkable differences in weight decrease curves and onset temperatures of thermal decomposition were observed between the two groups, Na-CMSs (1)-(3) and Na-CMSs (4)-(6). Upon heating, the C=O bonds based on carboxymethyl groups of Na-CMSs (1)-(3) were partially decomposed, although their structures were unclear. In contrast, the decomposition of C-O bonds based on intra- and inter- molecular ether linkages or hydroxyl groups in the glucose units was mainly observed for Na-CMSs (4)-(6). The increase of DS accompanied the increase of activation energy, but there was no significant difference in the activation energy among Na-CMSs (4), (5) and (6).

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Ambient concentrations of 7 mutagenic and/or carcinogenic polycyclic aromatic hydrocarbons (PAHs) were measured in Chiang Mai, Thailand, and compared to those in Tokyo. In Chiang Mai, airborne particulate samples were collected at two sites, i.e., commercial and residential sites (two stations in each site) from July through December in 1989. In Tokyo, sampling was carried out at a commercial/residential site in November 1989. PAHs were extracted by sonication, and analyzed by a multicolumn HPLC/computerized fluorometric detection system. Major observations are as follows ; 1) In both cities, ambient concentrations of PAHs and airborne particulates showed log normal distribution. Geometric mean/standard deviation is appropriate to express the situation of pollution. 2) In Chiang Mai, there was not a large difference in PAH concentrations between commercial and residential sites. This suggested wide-spreaded pollution over the city. On the other hand, concentrations of airborne particulates showed large differences among the sites. PAH concentrations in 1989 were higher than those in 1986. 3) Ambient concentrations of PAHs and airborne particulates concentrations were both low in the rainy season and high in the dry season in Chiang Mai. 4) Ambient concentrations of PAHs (except for rather volatile 4 ring PAHs) and airborne particulates in Chiang Mai were suggested to be higher than those in Tokyo. 5) In Tokyo, a fairly good correlation among concentrations of 7 PAHs and airborne particulates has been observed. In Chiang Mai, there has been good correlation among PAHs concentrations, but a poor correlation between PAHs and airborne particulate concentrations. This suggested that large content of rough particulates in Chiang Mai air may be higher than that in Tokyo. These results suggest that air pollution by PAHs and airborne particulates may be more serious in Chiang Mai than in Tokyo. Size distribution of airborne particulates seems to be different between these two cities.

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The effect of supplementing methionine (1%) to a 24.8% protein diet (normal protein diet, NPD) or a 7.5% protein diet (low protein diet, LPD) on the fate of methylmercury (MeHg) was investigated after oral administration of MeHg (20 μmol/kg). Hg concentration in the brain was increased by methionine supplement to LPD, but not to NPD. Methionine supplement to both NPD and LPD resulted in increased Hg concentration in the liver but decreased Hg concentration in the kidney. Hg concentrations in the blood and plasma were decreased only by methionine supplement to LPD. Urinary Hg excretion was increased by methionine supplement to both diets, whereas no marked difference in fecal Hg excretion was observed by the supplement. Hg concentration in the plasma low molecular weight (LMW) fraction 2 h after oral administration of MeHg (20 μmol/kg) was increased by methionine supplement to LPD, but not to NPD. This suggests that the ratio of availability of sulfur amino acids for the synthesis of protein to those for the synthesis of LMW thiol compounds may be affected by dietary levels of protein and methionine. As a result, the increased Hg concentration in the plasma LMW fraction would result in higher brain Hg concentration, since the brain uptake of ¹⁴C-L-phenylalanine was not affected by methionine supplement. The present results suggest that the effects of methionine supplement on the fate of MeHg depend, at least partly, on dietary protein levels.

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The oxy-radical scavenger, 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO), reduced the X-ray-induced mutant spot frequency. The inhibitory effect may be due to the scavenging of oxy-radicals in vivo by DMPO.

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In order to estimate metabolic bone condition, urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and urinary calcium, as well as serum Pyr and osteocalcin were tested as biochemical markers for bone metabolism in elderly in-patients who do not have metabolic bone disease, but rather, cerebrovascular disease. All the patients recruited in this study were divided into two groups of each sex, according to their mobility : the "able to walk without assistance"(W group) or the "could not walk independently"(NW group). Serum Pyr, urinary Pyr and D-Pyr of the NW group were significantly higher than those of the W group in the females, and a similar trend was observed among the male subjects. The levels of serum osteocalcin, one of the bone formation markers tested, showed no statistical difference between W and NW group in either sex. Patients 70-79 years old were selected from the above determined groups, and their serum Pyr, and urinary Pyr, D-Pyr and calcium were periodically determined and compared. In both sexes of the NW group, these markers were higher and increased over time than those of the W group. These results suggest that bone resorption in the NW group in both sexes accelerates over time and their fracture risk, therefore, increases, even if they have no metabolic bone disease.

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