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Biomedical subjects

E Kamata

Publications and source records attributed to E Kamata.

At least 19 recordsLinked to original sources

[A study of the relationships between exposure periods and no-effect doses in repeated dose toxicity tests].

In the risk assessment of chemicals to humans, it is a very important step to determine no-observed-adverse-effect-levels (NOAEL) or lowest-observed-adverse-effect-levels (LOAEL) from animal experiments. Recently, short-term screening tests, such as 28-day repeated dose toxicity test, are carried out in accordance with the regulative guidelines for the safety evaluation of chemicals. However, many problems still remain in the risk assessment to human based on short-term toxicity studies. For this reason, we studied the relationships between the exposure periods and NOAELs or LOAELs in repeated dose toxicity tests using available test results of 18 halogenated compounds. The ratios between each NOAEL or LOAEL of short-term tests (14, 28 days, 13 weeks and 6 month) and those of long-term tests (longer than one year) were calculated on the basis of same animal species, route and toxic effect. From this study, it was considered that exposures above 13 weeks were needed to satisfy the present safety factor considerations for setting an acceptable daily intake (ADI).

Administration, Inhalation

The expert system for toxicity prediction of chemicals based on structure-activity relationship.

The prediction systems of chemical toxicity has been developed by means of structure-activity relationship based on the computerized fact database (BL-DB). Numbers and ratio of elements, side chains, bonding, position, and microenvironment of side chains were used as structural factors of the chemical for the prediction. Such information was obtained from the BL-DB database by Wiswesser line-formula chemical notation. In the present study, the Salmonella/microsome assay was chosen as indicative of the target toxicity of chemicals. A set of chemicals specified with mutagenicity data was retrieved, and necessary information was extracted and transferred to the working file. Rules of the relations between characteristics of chemical structure and the assay result are extracted as parameters for rules by experts on the rearranged data set. These were analyzed statistically by the discriminant analysis and the prediction with the rules were evaluated by the elimination method. Eight kinds of rules to predict Salmonella/microsome assay were constructed, and currently results of the assay on aliphatic and heterocyclic compounds can be predicted as accurately as +90%.

Algorithms

[A study on the usefulness of the OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)].

We studied the usefulness of the OECD combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox) using cyclophosphamide (CP), which is well known for its toxicological properties. CP was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague-Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body weight and food consumption were observed in males given 6.7 mg/kg and in all treated females. One, 3 and 12 females died during pregnancy in the groups given 3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group. Leukopenia and anemia were evident in treated males. The thymus and spleen weights were significantly decreased in treated rats. Histopathologically, atrophy of the thymus, spleen and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss and postnatal death of pups were found in treated dams. The body weight of pups from treated dams was significantly lowered. Thus, most of the known toxicological properties of CP regarding systemic toxicity and reproductive/developmental toxicity were clearly demonstrated in this study. Therefore ReproTox can be considered a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume, although teratogenic potential and adverse effects on spermatogenesis and fertility were not detected under the present experimental conditions.

Administration, Oral

Sex difference in inhalation toxicity of p-dichlorobenzene (p-DCB) in rats.

The organ distribution and toxicity of p-dichlorobenzene (p-DCB) were compared in male and female rats after inhalation of 500 ppm of p-DCB for 24 h in a whole-body chamber. Concentrations of p-DCB in the serum, liver, kidney and fatty tissues were measured by gas chromatography at intervals during and up to 24 h after the treatment. Though no significant differences in the serum levels were observed between male and female rats, the p-DCB values in the livers of female rats were significantly higher than those of male rats. Conversely, significantly higher levels were found in the kidneys of male than of female rats. The distribution results thus appeared to correlate with the fact that nephrotoxic changes were observed only in male rats and that the appearance of minor hepatotoxic changes was limited to females.

Adipose Tissue

[Study on essential metal concentration in the organs of rats (report 1)].

Concentration of 5 elements (Ca, Cu, Fe, Mg, Zn) in 10 organs (brain, heart, lung, liver, kidney, spleen, testis, thymus, salivary gland and bone) and serum of rats were determined by inductively-coupled argon plasma atomic emission spectrometry (ICP). Samples were digested with nitric acid and perchloric acid in a sealed double Teflon vessel with polypropylene jacket by heating with a microwave oven. The concentration of 5 elements in the organs can be grouped into 5 categories as follows. (1) heart, liver and spleen (Mg > Fe > Ca > Zn > Cu) (2) lung and kidney (Mg > Ca > Fe > Zn > Cu) (3) brain, thymus and testis (Mg > Ca > Fe = Zn > Cu) (4) serum and bone (Ca > Mg > Fe = Zn > Cu) (5) salivary gland (Ca = Mg > Fe > Zn > Cu).

Animals

[Twenty-eight-day repeated dose toxicity test for tetrachlorvinphos in Wistar rat].

A 28-day oral toxicity test of tetrachlorvinphos (TCV) was conducted in male and female Slc: Wistar rats by gavage at dose levels of 0, 10, 100 or 1000 mg/kg/day. The male and female rats showed dose-related inhibition of serum cholinesterase activity and erythrocyte acetylcholinesterase activity. At a dose of 1000 mg/kg, body weight gain was decreased in males, and there were 6 deaths in females. Adrenal gland, liver, kidney and thyroid gland weights were increased. The adrenal lesions were characterized by vacuolization and swelling of the cortex cells. The hepatic lesions consisted of vacuolization and necrosis of the hepatocytes. The renal lesions consisted of regeneration and necrosis of the tubular epithelial cells. These lesions were mostly observed at a dose of 1000 mg/kg. After a 14-day recovery period in the 1000 mg/kg group, the changes of cholinesterase, total cholesterol, gamma-glutamyltransferase, alkaline phosphatase, aspartate aminotransferase and blood urea nitrogen in serum were restored or showed a tendency toward recovery. However, the lesions in the kidney and adrenal remained. More than 14 days are therefore considered to be needed for recovery. At doses of more than 10 mg/kg, significant inhibition of the serum cholinesterase activity in both sexes, erythrocyte acetylcholinesterase activity in males, and lesions of the adrenal gland in females were observed. Target organs for TCV-treated rats were the adrenal, liver and kidney. It was concluded that the NOEL under this experimental condition is less than 10 mg/kg/day.

Administration, Oral

[Acute and subacute toxicity studies of tris (1,3-dichloro-2-propyl) phosphate on mice].

Slc/ddY mice (10 male, 10 female per group) were given a single p.o. intubation of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) in olive oil and were observed for 14 days. LD50 values of male and female mice were 2.67 (2.52 approximately 2.83) and 2.25 2.25 (2.12 approximately 2.39) g/kg, respectively. The animals revealed ataxic gait, hyperactivity, and convulsion. Slc/ddY mice (12 male, 12 female er group) were administered diet containing 1.33, 0.42, 0.13, 0.04, and 0.01% of TDCPP for 3 months. Male and female mice of the 1.33% group showed emaciation, rough hair, and tremor; and all animals died within one month. Hematological studies showed slight anemia in males of the 0.42% group and females of the 0.42% and 0.13% groups. They also exhibited a tendency to increase ALP and GPT levels. The animals of the 0.42%, 0.13% and 0.04% groups exhibited tendency to increase liver weights and kidney weights in both sexes. Histopathologically, very slight focal necrosis was recognized in the liver in only 2 females of the 0.42% group. The NOEL under this condition is 0.01% in the diet of tris (1,3-dichloro-2-propyl) phosphate (male: 13.2 mg/kg/day, female: 15.3 mg/kg/day).

Administration, Oral

[Toxicity of 2-mercaptobenzothiazole in mice].

2-mercaptobenzothiazole (MBT) has been used mainly as a vulcanization accelerator in rubber manufacture and an intermediate in the production of other accelerators. Acute and chronic toxicity studies were performed to evaluate its potential to induce toxicological effect using Slc:ddY mice. The oral LD50 values of MBT (mg/kg) were as follows: (1) suspension in 5% gum arabic solution: 1558 for males and 1490 for females. (2) suspension in olive oil: 3148 for males. Convulsion was the major change in general conditions observed. The acute toxicity of MBT in males was stronger when suspended in 5% gum arabic solution than that when suspended in olive oil. A 20-month chronic toxicity study of MBT on mice was carried out with dose levels of 30, 120, 480 and 1920 ppm in the diet. Inhibition of body weight gain was observed in the 1920 ppm group of the males from the initial stage of treatment. Histopathologically, cell infiltration in the interstitium of kidney in the 1920 and 480 ppm groups of the males were found at 20th month. It was concluded that no observable effect level of MBT was 120 ppm (14.6 mg/kg/day for males and 13.52 mg/kg/day for females).

Administration, Oral

Comparison of the toxicity of p-dichlorobenzene (p-DCB) administered to male F344 rats orally or by the inhalation route.

The organ distribution and toxicity of p-DCB were compared in rats after either inhalation or oral administration. Male F344 rats were exposed to 500 or 125 ppm for 24 hr in a whole body inhalation chamber (H and L groups) or received a single dose of 300 mg/kg by gavage (PO group). The concentrations of p-DCB in the serum, liver, kidney and fatty tissues were measured by gas chromatography at intervals during and up to 24 hr after the treatment. Peak serum values for the L and H groups were lower than in the PO animals, but the organ/serum distribution ratios of p-DCB tended to be higher, in some cases markedly, in rats receiving the inhalation treatment. Significant increases in the levels of blood urea nitrogen, hepatic glutamic oxaloacetic transaminase and glutamic pyruvate transaminase and significant decreases in the levels of serum total cholesterol were observed only in the inhalation groups. Microscopically, the appearance of numerous eosinophilic droplets, together with swelling and desquamation of the proximal tubular epithelium of the kidney was especially noteworthy in H and L p-DCB treated groups. Thus, both biochemical and histopathological abnormalities induced by p-DCB were more pronounced in rats administered the compound by the inhalation route.

Administration, Inhalation

Radical surgical cure of Wolff-Parkinson-White syndrome: the Kanazawa experience.

Between 1973 and 1983, we operated on 160 patients with Wolff-Parkinson-White syndrome at Kanazawa University Hospital; 126 had Wolff-Parkinson-White syndrome alone, and 34 had combined cardiac diseases. Of the 160 patients, 140 were completely cured; postoperatively, they had no delta wave on electrocardiograms and no tachycardia attacks. In 11 patients, the delta wave reappeared an average of 56 days after operation. They, and three other patients with concealed Wolff-Parkinson-White syndrome, experienced several postoperative episodes of tachycardia. However, in 12 of the 14 patients with postoperative tachycardia attacks, these disappeared completely in the course of a long follow-up period and these patients are also considered to be cured symptomatically. In the two remaining patients, the tachycardia attacks persisted. Of the 126 patients with Wolff-Parkinson-White syndrome alone, none died as a direct result of the operation. Patients with combined cardiac diseases other than cardiomyopathy, mild Ebstein's anomaly, or venous abnormality were treated in one operation. Six of the 34 patients with combined cardiac diseases died. In none of the 160 patients was the His bundle intentionally interrupted as an alternative method of interrupting the accessory conduction pathway. Our study showed that life-threatening arrhythmias occur more often than expected in patients with Wolff-Parkinson-White syndrome and the tolerance for tachycardia attacks differs from patient to patient. Because the surgical treatment of Wolff-Parkinson-White syndrome is safe and reliable, as indicated in this report, the radical correction of this disease should be considered in carefully evaluated patients.

Adolescent

Effect of feed restriction on the peripheral blood and bone marrow cell counts of Wistar rats.

The effects of 33% and 66% restricted feeding on body and organ weights, and hematological and bone marrow cellular findings in rats were investigated. The body weight gains were suppressed by restriction of feed amount and the body weights of 66% restricted-feeding groups were almost unchanged for three months (110 g in males and 80 g in females). Marked organ weight reduction (both absolute and relative) was found in the liver and thymus of rats of both sexes. Neutrophils and lymphocytes in the peripheral blood were reduced. Reticulocytes in the 66% restricted groups were decreased to 1/4 of the control values at one month, but recovered slightly thereafter. Nucleated cell counts in bone marrow in the 66% restricted groups were decreased to 1/3 of the control values after three months. Thus, the most important effect of feed restriction seemed to be on bone marrow cells rather than on peripheral blood cells except for the reticulocytes. There was no significant difference between males and females.

Animal Feed