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d Pollution in the Watarase River caused by min- eral wastewater containing high levels of copper dis- charged during the development of the Ashio Copper Mine is one of the most well-known environmental pollution problems in Japan, and has been called the "Starting line of environmental pollution problems in Japan." In this study, we conducted follow-up investi- gations on the conditions of pollution in the Watarase River since 1991, and measured the heavy-metal lev- els in water in other rivers near the Watarase River and in soils around them. In addition, we compared the results in this study with previous results, i.e. pol- lution conditions in the Watarase River, other rivers and soils. Six points in upstream sites of the Watarase were chosen for sampling. Six samples from river wa- ter, five samples from soils around the respective points, and three samples from tap water distributed there were collected for the analysis. Heavy metal levels in rivers and soils around the Ashio Copper Mine were significantly lower than the environmental standards for them. When compared with our previous investi- gations, the levels of polluting heavy metals around the closed refinery at the Ashio Mine were gradually but clearly reduced. In conclusion, the environment around the Watarase River has been steadily improved so that safety in the living environment is assured.

In the gross anatomy laboratory, which is one of the compulsory subjects in most medical and dental schools, participants cannot avoid exposure to formaldehyde (FA), which is emitted from cadavers during dissection. FA has been recognized as a harmful chemical and we have previously reported that symptoms felt by participants in a gross anatomy laboratory are similar to those of allergic diseases. Although immunoglobulin E (IgE)-mediated sensitization to FA is a matter of controversy, it is possible that IgE production is evoked during a gross anatomy laboratory and is responsible for the reported symptoms. In order to test this hypothesis, we examined the relationships between the personal FA exposure levels and plasma IgE levels in a gross anatomy laboratory. In the laboratory, the personal FA exposure levels ranged from 0.33 to 1.47 ppm. Total blood IgE levels did not increase significantly and specific IgE to FA was negative during the laboratory sessions. Thus, from this study, we cannot support the hypothesis that the exposure to FA triggers an IgE-mediated reaction in this study. In conclusion, exposure to FA does not induce IgE production during gross anatomy laboratories at our school.

Goal, Scope and Background Cadavers for gross anatomy laboratories are usually prepared by using embalming fluid which contains formaldehyde (FA) as a principal component. During the process of dissection, FA vapors are emitted from the cadavers, resulting in the exposure of medical students and their instructors to elevated levels of FA in the laboratory. The American Conference of Governmental Industrial Hygienists (ACGIH) has set a ceiling limit for FA at 0.3 ppm. In Japan, the Ministry of Health, Labour and Welfare has set an air quality guideline defining two limit values for environmental exposure to FA: 0.08 ppm as an average for general workplaces and 0.25 ppm for specific workplaces such as an FA factory. Although there are many reports on indoor FA concentrations in gross anatomy laboratories, only a few reports have described personal FA exposure levels. The purpose of the present study was to clarify personal exposure levels as well as indoor FA concentrations in our laboratory in order to investigate the relationship between them.

A simple and rapid method for the simultaneous determination of seven golf course pesticides in aqueous samples was developed by using in-tube solid-phase microextraction (in-tube SPME) coupled with liquid chromatography. In-tube SPME, in which the analytes were extracted from the sample directly into an open capillary column, is an extraction technique for organic compounds in aqueous samples. Although an open tubular capillary column with a thick film of polymer was used for the conventional in-tube SPME, we used a porous-layer open-tabular (PLOT) column in which there was a porous layer on the inner wall and has a larger surface area. A microsyringe pump equipped with a gastight syringe was employed to sequentially pump the sample solution through the capillary. The detection limits were from 0.9 to 4.1 ng ml-1. The calibration curves were linear in the range from 1 to 50 ng ml-1. We took a survey of seven golf course pesticides in several water samples by using the developed method.

Two unidentified arsenic metabolites were detected in the liver of rats on a gel filtration column by HPLC inductively coupled argon plasma mass spectrometry after an injection of dimethylarsinic (DMA(V)), dimethylarsinous (DMA(III)), monomethylarsonic (MMA(V)), or monomethylarsonous (MMA(III)) acid. The same arsenicals were also produced in vitro by incubation of DMA(III) in the liver supernatant but not by DMA(V). The two arsenic metabolites eluted at the same retention times as those of the two arsenicals prepared by reaction of DMA(V) with either thiosulfate plus disulfite or hydrogen sulfide or sodium sulfide plus sulfuric acid. The faster and slower eluting products on a gel filtration column were assigned as dimethyldithioarsinic acid (dimethylarsinodithioic acid) (DMTA(V)) and dimethylthioarsinous acid (DMTA(III)) from mass spectrometric data at m/z = 170 and 138 by electrospray ionization mass spectrometry with negative and positive ion modes, respectively. They were prepared selectively by reacting DMA(V) with hydrogen sulfide or sodium sulfide plus sulfuric acid under different reaction conditions. DMA(III) but not DMA(V) was transformed to DMTA(III) and DMTA(V) in the presence of sodium sulfide in vitro, suggesting that DMA(V) is reduced to DMA(III) with hydrogen sulfide, thiolated to DMTA(III), and then further thiolated oxidatively to DMTA(V). Metabolically, it is assumed that DMA(III) is transformed to DMTA(III) in the presence of sulfide ions, and then, DMTA(III) is oxidatively thiolated to DMTA(V). As the chemical species produced by reduction with the Reay and Asher method are DMTA(III) and DMTA(V), and different from DMA(III), the studies carried out with DMA(III) with the Reay and Asher method have to be reexamined.

Alkylphenols and bisphenol A (BPA) in rivers in Chiba City were determined by gas chromatography-mass spectrometry (GC-MS) after extractive derivatization with ethyl sulfate. The relevance of the use of areas and their concentrations was investigated. Nonylphenol (NP) concentrations in the rivers in the surveyed areas ranged from 0.2 to 24μg·l-1, exceeding the No-Observed-Effect Concentration (NOEC) value (6.08μg·l-1). 5800μg·kg-1 NP and 170μg·kg-1 BPA were observed in bottom sediments from Hanamigawa and Yoshikawa, respectively. These values suggested NP and BPA accumulation in these rivers.

Pulmonary responses to ozone exposure (1.0 ppm) were investigated in mice sensitized to ovalbumin compared with control mice receiving saline. Pulmonary function parameters were measured by pneumotachography. Arterial blood gases and the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and tumor necrosis factor(TNF-) in bronchoalveolar lavage fluid were analyzed. Ozone exposure, when compared with filtered air exposure, caused significantly larger decreases in dynamic compliance (P 0.05) and minute ventilation (P 0.05) in ovalbumin-sensitized mice but not in control mice. Moreover, the decrease in minute ventilation in response to ozone exposure was significantly greater (P0.01) in ovalbumin-sensitized mice than in control mice. Ozone exposure caused a significant decrease in PaO2 in ovalbumin-sensitized mice but not in control mice. PaO2 after ozone exposure tended to be smaller in ovalbumin-sensitized mice than in control mice. The concentration of sICAM-1 in bronchoalveolar lavage fluid increased in ovalbumin-sensitized mice, but effects of ozone exposure were not observed. These results indicated that sensitization of the immune system to ovalbumin might be a risk factor which aggravates the effects of ozone exposure on the respiratory system. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

The metabolic pathways for arsenic were precisely studied by determining the metabolic balance and chemical species of arsenic to gain an insight into the mechanisms underlying the animal species difference in the metabolism and preferential accumulation of arsenic in red blood cells (RBCs) in rats. Male Wistar rats were injected intravenously with a single dose of arsenite (iAs(III)) at 2.0 mg of As/kg of body weight, and then the time-dependent changes in the concentrations of arsenic in organs and body fluids were determined. Furthermore, arsenic in the bile was analyzed on anion and cation exchange columns by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). The metabolic balance and speciation studies revealed that arsenic is potentially transferred to the hepato-enteric circulation through excretion from the liver in a form conjugated with glutathione (GSH). iAs(III) is methylated to mono (MMA)- and dimethylated (DMA) arsenics in the liver during circulation in the conjugated form [iAs(III)(GS)(3)], and a part of MMA is excreted into the bile in the forms of MMA(III) and MMA(V), the former being mostly in the conjugated form [CH(3)As(III)(GS)(2)], and the latter being in the nonconjugated free form. DMA(III) and DMA(V) were not detected in the bile. In the urine, arsenic was detected in the forms of iAs(III), arsenate, MMA(V), and DMA(V), iAs(III) being the major arsenic in the first 6-h-urine, and DMA(V) being increased in the second 6-h-urine. The present metabolic balance and speciation study suggests that iAs(III) is methylated in the liver during its hepato-enteric circulation through the formation of the GSH-cojugated form [iAs(III)(GS)(3)], and MMA(III) and MMA(V) are partly excreted into the bile, the former being in the conjugated form [CH(3)As(III)(GS)(2)]. DMA is not excreted into the bile but into the bloodstream, accumulating in RBCs, and then excreted into the urine mostly in the form of DMA(V) in rats.

This report reviews the biological effects and case reports of suicidal or accidental ingestion of, and occupational exposure to sodium azide. Ingested doses of sodium azide were estimated for the 6 survival and 4 fatal cases studied. The lowest dose among survival cases was 5-10 mg. The patient reported headache, sweating, and faintness within approximately 5 minutes of ingestion. Four victims ingested 20 to 40 mg and recovered within 2 hours. However, a man who took 80 mg reported chest pain for 6 months after ingestion. The smallest doses among fatal cases were 0.7-0.8 g for women and 1.2-2 g for men. All victims suffered from hypotension, tachycardia, hyperventilation, diaphoresis, vomiting, nausea, and diarrhea. There is no antidote for sodium azide. Detoxicants for cyanide such as sodium nitrite or thiosulfate were tried, but were unfortunately, ineffective. Sodium nitrite may worsen the hypotension caused by sodium azide, and is not recommended. Occupational exposure to sodium azide is thought to be common, however, fatal exposure is rare. NIOSH "Recommended Exposure Limits" for sodium azide is 0.3 mg/m3.

Both organic and inorganic forms of selenium (Se) can be utilized in the body, and the biotransformation of selenite into an organic form of Se in the bloodstream is the first step for the utilization of inorganic Se. Selenite injected intravenously into rats was shown to be taken up rapidly and selectively by red blood cells (RBCs) through the anion-exchange carrier. The uptake of selenite by RBCs was inhibited by 4,4'-diisothiocyano-2,2'-stilbene disulfonate, a specific inhibitor of the anion-exchange carrier (band 3 protein). The uptake was also inhibited by chromate owing to the glutathione deprivation in RBCs, which was confirmed by the inhibition by azodicarboxylic acid bis(dimethylamide). The presence of hydrogencarbonate in the incubation solution slightly retarded the uptake of selenite by RBCs. Although Se effluxed into the plasma was bound selectively to albumin, plasma proteins (albumin) did not accelerate the uptake process. Based on these results, the rapid and selective uptake of selenite by RBCs was explained by the selective and efficient uptake through the anion-exchange carrier, followed by reduction by glutathione.

Copper (Cu) was selectively removed from metallothionein (MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color) in vivo and in vitro by tetrathiomolybdate (TTM). Female LEC rats were injected intraperitoneally with TTM at a dose of 10 mg/kg body weight for 8 consecutive days. More than 2 3 of the Cu accumulating in the liver was removed by TTM treatment 24 h after the last injection. Although most Cu was bound to MT in the soluble fraction before TTM treatment, the Cu remaining in the liver was present almost exclusively in the nonsoluble fraction together with molybdenum (Mo). Cu,Zn,Cd-MT was separated from the liver of LEC rats that had been injected with cadmium (Cd) and reacted with TTM at mol ratios of 0, 0.25, 0.50, 1.0, 2.0 and 4.0 to Cu bound to MT for 10 min at 37 °C. When TTM was added at a mol ratio of less than 1.0, a Cu,Zn,Cd-MT/TTM complex was detected, while addition of TTM at a mol ratio of greater than 1.0 selectively removed Cu from MT and produced a Cu/TTM complex via liberation of Zn,Cd-MT from the Cu,Zn,Cd-MT/TTM complex. Excessive TTM appeared to facilitate polymerization of the Cu/TTM complex to insoluble polymers. The dose-related formation of differing MTATTM complexes explains the findings observed in vivo.

Summary Chelation therapy with tetrathiomolybdate (TTM) was applied to Long- Evans rats with a cinnamon coatcolor (LEC rats), an animal model for Wilson disease, to remove copper (Cu) accumulated in the liver in a form bound to metallothionein (MT). Changes in molybdenum (Mo) and Cu concentrations and their biological forms in serum of LEC rats determined at different times after a single intraperitoneal injection were compared with those of Wistar (normal) rats. The change in Mo concentration in serum of normal rats was mono-phasic, whereas in LEC rats it was bi-phasic. The phase in normal rats and the first phase in LEC rats appeared to reflect the process of uptake and disappearance of TTM in the livers of Wistar and LEC rats. On the other hand, the second phase in LEC rats paralleled the changes of Cu and appeared to reflect the complex formation (Cu/ thiomolybdate complex) between Mo and Cu accumulated in the liver. The complex was specifically bound to albumin as determined by high performance liquid chromatography with inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). The results suggested that the changes in the Mo concentration in serum reflected the amount of Cu in the liver.

Mass spectrometry with inductively coupled argon plasma excitation (ICP-MS) was used as a multi-element specific detection method for HPLC for the speciation of selenium (Se) in biological samples. Se-containing biological constituents were separated on a size-exclusion column and were detected Se-specifically at m/z 78 and 82 for natural abundance 78Se and 82Se, respectively. Se peaks not identical with known authentic samples were detected. Diets with different Se contents induced changes in the distributions of Se-containing constituents more in urine, kidney and liver samples than in plasma and red blood cells samples. The results indicate that HPLC-ICP-MS is a specific and sensitive means for the speciation of Se-containing biological constituents.

Objectives: The chlorination of river water in purification plants is known to produce carcinogens such as trihalomethanes (THMs). We studied the river system of the Watarase, Tone, and Edo Rivers in regard to the formation of THMs. This river system starts from the base of the Ashio copper mine and ends at Tokyo Bay. Along the rivers, there are 14 local municipalities in Gunma, Saitama, Ibaragi and Chiba Prefectures, as well as Tokyo. This area is the center of the Kanto plain and includes the main sources of water pollution from human activities. We also analyzed various chemicals in river water and tap water to clarify the status of the water environment, and we outline the problems of the water environment in the research area (Fig. 1).Methods: Water samples were taken from 18 river sites and 42 water faucets at public facilities in 14 local municipalities. We analyzed samples for volatile organic compounds such as THMs, by gas chromatography mass spectrometry (GC-MS), and evaluations of chemical oxygen demand (COD) were made with reference to Japanese drinking water quality standards.Results: Concentrations of THMs in the downstream tap water samples were higher than those in the samples from the upperstream. This tendency was similar to the COD of the river water samples, but no correlation between the concentration of THMs in tap water and the COD in tap water sources was found. In tap water of local government C, trichloroethylene was detected.Conclusions: The current findings suggest that the present water filtration plant procedures are not sufficient to remove some hazardous chemicals from the source water. Moreover, it was confirmed that the water filtration produced THMs. Also, trichloroethylene was detected from the water environment in the research area, suggesting that pollution of the water environment continues.

The observed toxicity of arsenic is highly dependent on animal species and differences in metabolism. Rats are one of the most tolerant species, and the metabolic pathway is quite different in some aspects from those of other mammals. The distinct metabolic pathway including the preferential accumulation in red blood cells (RBCs) has been explained, whereby allowing an effective use of rats as an animal model for the arsenic metabolism. In the present study, distributions of arsenic among organs/tissues/body fluids and their chemical forms were studied after intravenous injection of arsenic in the forms of dimethylarsinic (DMA V ) and monomethylarsonic acids (MMA V ) to rats. DMA V and MMA V were mostly excreted into urine immediately after the injection as the intact forms, and both forms were taken up less effectively by organs/tissues than arsenite. The methylated arsenics distributed in organs/tissues were excreted directly into urine and excreted before being redistributed in RBCs. DMA V and MMA V taken up by the liver were transformed to metabolites not yet identified, accumulated transiently in the liver, and then they disappeared from the liver. The unidentified metabolites were assumed to be transformed from dimethylarsinic acid (DMA III ) following the consecutive metabolic reactions [MMA V → monomethylarsonous acid (MMA III ) → DMA V → DMA III ]. The unidentified metabolites were excreted not into the bile but into the bloodstream. Injections of DMA V and MMA V induced a biliary excretion of arsenic but only at 0.2–0.3% of the dose, the arsenic in the bile being their intact free forms.

Publisher Summary Diverse chemical species of arsenic (As) are taken up by humans through dietary foods and water. The most important chemical species from the viewpoint of the toxicity and exposure to humans are arsenite (iAsIII) and arsenate (iAsV). Because the inorganic As absorbed in the body is excreted in the urine mostly in the form of dimethylated arsenic (DMA), the toxicity of As must be caused by one of the metabolites during its transformation. Arsenite (As) absorbed by the body is believed to be transferred to the liver, and then it is transformed by consecutive methylation and reduction reactions to DMA. iAsIII is oxidatively methylated to monomethylarsonic acid (MMAV) and then reduced to monomethylarsonous acid (MMAIII) for further oxidative methylation to dimethylarsinic acid (DMAV). In rats, DMAV is reduced efficiently to dimethylarsinous acid (DMAIII) and then excreted into the bloodstream, where DMAIII is sequestered selectively by erythrocytes, resulting in the selective accumulation of As in erythrocytes in rats.

In order to know the element levels in the urine of patients with chronic arsenic poisoning caused by arsenic assimilated from burning coal via air and food, we investigated various elements in the urine of 16 patients with this disease and 16 controls living in the same county in Guizhou Province of China. Concentrations of 25 elements (Al, As, Ba, Be, Bi, Ca, Cd, Cr, Cu, Fe, Ga, Mg, Mn, Mo, Ni, P, Pb, Rb, Sb, Se, Sn, Sr, Ti, V and Zn) were determined by an inductively coupled plasma mass spectrometer or an inductively coupled plasma atomic emission spectrometer. The average concentrations of Cu, Ga and Sn as well as As in the patients were significantly higher, and those of Cr, Rb, Sr and Ti in the patients were significantly lower than the control values. Al, Ba, Mn, Ni and Se were under detection limit in the patients, though they could be detected in the controls. There were no positive correlations between the concentration of As and the concentrations of other elements, including Cu, Ga and Sn in the patients. The results of this study suggest that As from burning coal might influence the urinary excretion of some elements.

The disposition of selenium (Se) was investigated in Wistar rats of various Se status after an intravenous injection of 82Seselenite. Various fractions of plasma, urine, and cytosols from liver and kidney were separated by high performance liquid chromatography (HPLC), coupled with an inductively coupled argon plasma-mass spectrometry (ICP-MS). The technique allowed simultaneous differentiation of the fate of injected and endogenous Se, and if it was influenced by the previous Se burden in the tissues. A broad Se-peak from plasma was resolved in two fractions by assessing the m z 82 78 ratios. Urinary profiles indicated that the metabolism of Se was dose-dependent; monomethylselenol being the primary metabolite of Se in untreated animals, whereas noticeable amount of trimethylselenonium ion was detected after the injection of 82Se. Liver and kidney cytosols contained complex Se-enriched fractions, a positive identification of which was not done in this study. In most cases, the enrichment of tissue fractions with the stable isotope was altered by the dietary Se levels, the isotope nevertheless was exchanged with the endogenous Se in various macromolecules to a varying degree.

Mutant Long-Evans rats with a cinnamon coat-color (LEC rats) have been established as an animal model for Wilson disease, a genetic disorder of copper (Cu) metabolism. Systemic disposition of molybdenum (Mo) and altered distributions of Cu were compared in eight organs between LEC rats and Wistar rats (normal) at different times after a single intraperitoneal injection of tetrathiomolybdate (TTM) for chelation therapy. Excretion through urine and feces was also examined. Hepatic disposition of Mo was dramatically increased in LEC rats, suggesting that the interaction of TTM with Cu results in enhanced uptake of Mo. Concentrations of Mo and Cu decreased in the liver of LEC rats over time, whereas those in the spleen increased. Although the concentration of Mo taken up by the kidney decreased over time after an initial increase in both rats, Cu concentration increased over time. Cu was not redistributed to the brain. Excretion of Mo through urine was decreased and that into feces was increased in LEC rats compared with those in Wistar rats. These results indicate that TTM is taken up by the liver depending on the Cu content, and the Cu and Mo removed from the liver are mostly excreted through feces. Redistribution of Cu was observed in the spleen and kidneys, but not in the brain.

High-performance liquid chromatography (HPLC) of biological fluids and tissue cytosolic preparations was employed in conjunction with argon-induced inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution of stable isotopes as tracers. The common way of presenting the data from the ICP-MS is by plotting the count rates versus the retention time of HPLC fractions. Additional information can be derived, e.g., the composite peaks can be further resolved, and the level of enrichment in various biological components can be expressed by alternative ways of presenting these data. The two additional approaches described here involve presenting the ratios of enriched tracer with a suitable naturally abundant mass number of the same element, and by expressing the extent of enrichment by the tracer isotope in a given fraction to that of the same mass number in the fraction derived from an untreated source. Each method of presentation has different merits and drawbacks. The data therefore may be best presented in more than one way to emphasize the conclusions from a given experiment. Observations are presented after simultaneously injecting stable isotopes of three essential elements, copper, selenium and zinc, into mice. Plasma and liver cytosolic fractions were analysed and data represented in different ways as indicated above.

An epidemiological study was performed on 1,815 cadmium-exposed and 240 nonexposed inhabitants of the Kakehashi River basin in Ishikawa, Japan. The significance of urinary cadmium concentration as an indicator of internal dose in a general environment polluted by cadmium was investigated. The mean urinary cadmium concentration (Cd-U) increased in a dose-related manner when the subjects were classified according to the average cadmium concentration in their village rice and according to their period of residence in the polluted area. As total cadmium intake increased, Cd-U also increased, and strong correlations were found (r = .93 in men and r = .88 in women). Therefore, it was concluded that, on a group basis, Cd-U is a useful indicator of the internal dose of environmental cadmium exposure.

In addition to the major urinary selenometabolite, 1β-methylseleno-N-acetyl-D-galactosamine (selenosugar), several minor selenometabolites were also detected in rat urine by high performance liquid chromatography–inductively coupled argon plasma mass spectrometry. One of them, in a partially purified urine sample, was generated from selenosugar under aerobic conditions and also transformed through oxidation by H2O2. It was identified as monomethylseleninic acid. Therefore, this urinary selenocompound should not be regarded as a naturally occurring metabolite but as a selenosugar artifact. Moreover, an additional selenometabolite was detected in the same urine sample. Although this selenometabolite has not been identified yet, it seems to contain monomethylselenyl group(s) because of its transformation to monomethylseleninic acid through oxidation. Thus, urine samples must be handled with care so as not to allow oxidation by air, to prevent transformation to artificial selenocompounds.

Daily cobalt chloride injection for three days produced a rise of basal blood glucose concentration accompanied by the elevation of basal insulin levels as well as glucose-stimulated insulin secretion in rabbits, while the sum of blood glucose concentration following oral glucose remained normal. Hypertriglyceridemia observed in cobalt-treated rabbits correlated highly with glucose-stimulated insulin secretion. Higher concentration of plasma FFA was observed in pair-fed control rabbits as comparedto the cobalt-treated rabbits.

The kinetics of plasma TG metabolism was assessed in ten rabbits with hypertriglyceridemia induced by injection of cobalt chloride and compared with normal ten pair-fed rabbits. Plasma TG turnover rate was remarkably higher in cobalt-treated than in control rabbits, while lipoprotein lipase activity in adipose tissue was similar in both groups. The relationship between the concentration and turnover rate of plasma TG in both groups of animals was expressed as an asymptotic regression y=31.91934(1-e-0.0034788x). Nine of ten cobalt-treated rabbits located in the 95% confidence belt around the curvilineal line suggesting that the hypertriglyceridemia in these rabbits was predominantly due to enhancement of of plasma production, while only one rabbit a decrease of the removal efficiency was suspected to be a contributing factor in abnormality. The plasma TG concentration correlated significantly with the change in TG turnover rate. In the cobalt-treated rabbits, the plasma FFA values were similar to that of the pair-fed control rabbits, while the hepatic TG levels were significantly lower than that of the control rabbits.

This investigation aimed at examining the hypertriglyceridemia induced by cobalt chloride may have some relationship with the increased plasma insulin and blood glucose level. The transitory rise of blood glucose at 2 hours after the intravenous injcation of cobalt chloride was synchronous with the increased level of blood insulin. Injection of cobalt chloride could not bring about higher concentration of plasma FFA than that of control rabbits, while at 24 hours after the injection, about a twentyfold increase of plasma triglyceride was observed accompanied by an accumulation of triglyceride in the liver. Hepatic α-glycerophosphate content was significantly already higher at 2 hours and this persisted for 24 hours whereas at 24 hours blood glucose returned to normal level with a slightly higher blood insulin level.Despite increased level of blood insulin, no significant change could be observed in hepatic cyclic AMP content at 2 hours and there was not very much change in hepatic lysosomal triglyceride lipase activity at 24 hours after the injection. Therefore, hypertriglyceridemia observed in the cobalt-treated rabbit may be caused not by insulin induced inhibition of lipolysis in existing hepatic triglyceride.

Radioisotopic kinetic studies of plasma triglyceride transport have been performed in rabbits treated with tetrachlorobiphenyls and compared with data obtained from untreated or olive oil-treated rabbits. Administration of tetrachlorobiphenyls provoked a rise of plasma triglyceride and an elevation of plasma triglyceride production rate but tended to lower the fractional turnover rate. The relationship of turnover rate to plasma concentration of triglyceride suggests that the increase of plasma triglyceride concentration observed in tetrachlorobiphenyl-treated rabbits can be accounted for by an increased production in some of cases, but in other cases glyceridemia is due primarily to a removal defect.