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Biomedical subjects

Y Nakaji

Publications and source records attributed to Y Nakaji.

At least 19 recordsLinked to original sources

[A 13-week toxicity study of simultaneous administration of cochineal and aluminum potassium sulfate in rats].

Cochineal (C), a scarlet material extracted from the powdered pregnant insect, Dactylopius Coceus Costa, is used as a color food additive in the form of aluminum lakes. A 13 week subchronic toxicity study was conducted to investigate the effects of simultaneous administration of C and aluminum potassium sulfate (A). Male and female Wistar rats (5-weeks-old, 15 rats/group) were given diets containing 0.75%A and 0.75%C (1.5%AC), 1.5%A and 1.5%C (3%AC), 3%C alone or 3%A alone. The following results were obtained. 1) No toxic symptoms or death occurred in any treated group. Body weight gain in male rats of the 3%A group decreased significantly. 2) Serum levels of phospholipids, triglycerides (TG) and total cholesterol in male rats and TG in female rats fed 3%C, 3%A or 3%AC were significantly decreased at the 13th week. The serum level of glutamate dehydrogenase (GIDH) in male rats treated with 1.5% or 3%AC was increased at the 4th week but no difference from control was observed at the 13th week. 3) No histopathological changes attributable to A and/or C administration were observed. In this 13-week oral toxicity study, no dose-dependent synergistic effects of simultaneous administration of C and A were found except for an increase in serum GIDH.

Administration, Oral

A method for identifying causative chemicals of allergic contact dermatitis using a combination of chemical analysis and patch testing in patients and animal groups: application to a case of rubber boot dermatitis.

A 63-year-old woman developed allergic contact dermatitis from rubber boots. Initial investigation, by patch testing in the patient and chemical analysis of the causative rubber boots, revealed that mercaptobenzothiazole (MBT) and dibenzothiazyl disulfide (MBTS) were the causative chemicals. Subsequent investigations were performed by patch testing in animal groups. An extract of the causative rubber boots, MBT and MBTS were used for sensitization of guinea pigs by the guinea pig maximization test (GPMT). 3 animal groups, A (with the boot extract), B (with MBT) and C (with MBTS) were successfully prepared. The boot extract was fractionated by column chromatography and thin-layer chromatography (TLC). Each fraction was subjected to patch testing in the animal groups. Positive reactions in all groups would show that the active fractions contained MBT-type compounds, whereas a positive reaction in group A but negative ones in group B and C would show that the active fractions did not contain any MBT-type compounds. Each fraction was then analyzed by gas chromatography (GC), GC-mass spectrometry (GC-MS), direct inlet-MS (DI-MS) and high-performance liquid chromatography (HPLC). By this investigation, we found not only known allergens (MBT, MBTS), but also unknown allergens: S-substituted MBT-type compounds and styrenated phenol (SP). Thus, SP was shown to be a candidate as a human sensitizer even though the patient did not react to it.

Allergens

[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

[Acute and subacute toxicity studies of Bis(2,3-dibromopropyl) phosphate magnesium in rat].

Acute and subacute oral toxicity tests of Bis(2,3-dibromopropyl) phosphate magnesium (Bis-BP.Mg) were carried out in Wistar rats. In the acute toxicity test, Bis-BP.Mg suspended in arabic gum was administered orally to a group consisting of 10 male and 10 female rats, and they were observed for 14 days. LD50 values of male and female rats were 283 (253 approximately 314) mg/kg and 261 (219 approximately 310) mg/kg, respectively. As toxic symptoms, eyelid closure, crouching, shivering and staggering gait were observed in the treated groups of both sexes. In gross findings, hypertrophy, discoloration and necrotic change of the liver, and hypertrophy and discoloration of the kidney were observed in the treated groups. In histopathological examination, necrosis, desquamation, large nuclei formation of the tubular epithelium, and tubular dilatation of the kidney and necrosis of the liver cells were observed in the treated groups. In the subacute toxicity test, groups of rats consisting of 5 males and 5 females were fed a commercial diet containing 0, 30, 100, 300 and 1000 ppm Bis-BP.Mg for 45 days. In body weight and food consumption, there were no significant difference between the control and treated groups. Significant increases were observed in the liver and kidney weights of male rats fed 1000 ppm Bis-BP.Mg. Histopathologically, desquamation, swelling, and large nuclei formation of the tubular epithelium and tubular dilatation of the kidney were observed, but they were much less frequent than those in the acute toxicity test. It was concluded that Bis-BP.Mg has apparent renal toxicity.

Administration, Oral

[Comparative studies on acute toxicity of glutaraldehyde using young and old rats].

Acute oral toxicity test of glutaraldehyde (GA) was carried out in young (5-6W) and old (57-60W) Wistar/ST rats. Experiment 1: Various doses of GA were administered by gavage. After 30 minutes, the rats showed abnormal gait, then took an abdominal or lateral position after 4 hours. Gross erosion, discoloration and thickening of the glandular stomach mucosa and hyperemia of the liver, intestine and lung were observed in the dead rats. The LD50 values were 283 mg/kg for young rats and 141 mg/kg for old rats. Experiment 2: One half of the LD50 doses (140 mg/kg and 70 mg/kg of GA) were administered to young and old rats by gavage, respectively. Both groups showed a similar toxicity. Organ weights were not changed. In gross findings, erosion, discoloration and thickening of the glandular stomach mucosa were observed on day 1-7, but these damages were recovered by day 14. Histopathologically, atrophy, degeneration, necrosis, hemorrhage, edema and cell infiltration of the glandular stomach mucosa were found on day 1. Recovery from these changes was observed from day 3. Changes in several serum enzyme activities were observed on day 1-3. Therefore, susceptibility to the acute toxic effect of GA was higher in old rats than in young rats. However, no apparent differences were observed in the toxic profiles by GA between young and old rats.

Administration, Oral

Phosgene (chlorophenyl)hydrazones, strong sensitizers found in yellow sweaters bleached with sodium hypochlorite, defined as causative allergens for contact dermatitis by an experimental screening method in animals.

12 young men developed allergic contact dermatitis from wearing yellow cotton sweaters. We attempted to identify the causative agents by an experimental screening method in animals. Guinea pigs were sensitized with an acetone extract of the sweater material, by means of the guinea pig maximization test (GPMT). Active ingredients were then separated from the extract, by step-by-step patch test screening of chromatographic fractions in the guinea pigs, and finally analyzed by gas chromatography-mass spectrometry (GC-MS). Although there were 2 allergens with important activity (1 in the fraction eluted from the silica gel column with hexane, and 1 in the methanol fraction), the present study is focussed on the fat-soluble allergens in the hexane fraction. GC-MS analysis revealed that 4 kinds of phosgene (chlorophenyl)hydrazones (PCPHs) were present in the hexane fraction. PCPHs prepared in our laboratory showed strong eliciting activities, not only in the guinea pigs sensitized with the extract, but also in a male volunteer sensitized by exposure to a yellow sweater during irritancy testing. Phosgene (2,5-dichlorophenyl)hydrazone, which was the main component among the PCPHs found in the sweater, sensitized guinea pigs even at the 1 ppm level. From these results, we conclude that PCPHs were one of the allergens responsible for the cases.

Animals

[Combined long-term toxicity/carcinogenicity test of alpha-bromocinnamic aldehyde (BCA) applied to female mouse skin].

Bromocinnamic aldehyde (BCA), an antibacterial/antifungal agent, was tested for its chronic toxicity/carcinogenicity in female Slc:ddY mice. The animals received 0.25%, 1.0% and 4.0% of BCA dissolved in olive oil applied to the shaved back skin area twice a week for 79 weeks. The control group received olive oil alone under similar conditions. In addition to these animals, 5 animals in each group were killed at 6 and 12 months for investigation of the time-related toxic effect of BCA. A slight inhibition of body weight increase and a slight decrease in the survival rate were seen in the 4.0% BCA-treated group. No significant changes were observed in hematological parameters at 6, 12 and 18 months. In chemical biochemistry determination in the blood at 6 and 12 months, a significant decrease in non-esterified fatty acid and phospholipid values was observed in the experimental groups. Histopathologically, necrosis, scabbing, cell infiltration and thickening of the epidermis were noted at the site of application in the 4.0% BCA group. Moreover, extramedullary hematopoiesis and amyloid degeneration were detected in the spleen, while the incidence of adenomas in the lung decreased with a dose-response. These changes seemed to be the result of a non-specific inflammatory reaction to the irritation effects of the agent on the skin. No significant differences in the incidence of tumors were found between the control and experimental groups, not only at the site of application but also in other organs, although lung adenomas decreased dose-dependently in all treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes

[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

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

Acute toxicity tests on 113 environmental chemicals.

Acute toxicity tests on 113 environmental chemicals were conducted by the order of the Japanese government agencies. the LD50s or LC50s for 23 household chemicals, 11 medical drugs, 10 drug additives, 20 food additives, 13 industrial chemicals, 14 environmental pollutants, 12 agricultural chemicals and 5 organic solvents are presented together with the major toxic signs and symptoms and macroscopic changes in tissues. These toxicity data will be useful as an information source for regulatory purposes and also for prediction of the potential for acute toxicity of a wide variety of new chemicals.

Animals

Nephrotoxic effect of tris(2,3-dibromopropyl)phosphate on rat urinary metabolites: assessment from 13C-NMR spectra of urines and biochemical and histopathological examinations.

Rats received either single oral doses of 0, 25, 50, 100 and 200 mg/kg tris(2,3-dibromopropyl)phosphate (Tris-BP) or repeated doses of 50, 100 and 200 mg/kg/day Tris-BP for 7 days. Urine was collected over a 24-hr period and subjected to 13C-NMR and biochemical examinations. Tris-BP produced significant increases of urinary glucose and lactate. Urinary gamma-glutamyltransferase, lactate dehydrogenase and alkaline phosphatase levels were significantly elevated on the first 2 days of post-treatment. Histopathologically, the kidney exhibited proximal tubular damage at a dose of 200 mg/kg. There was a good correlation among the histopathological, biochemical results, and the 13C-NMR urinary metabolite fingerprints in the assessment of Tris-BP-induced renal damage. The abnormal patterns of metabolite excretion suggested that the lesions produced by Tris-BP were caused by changes in the metabolic function of tubular epithelial cells. The urinary excretion of lactate, enzymes and inhibition of glucose reabsorption from the tubular lumina may be attributed to necrosis and desquamation of the tubular cell.

Animals

Short-term toxicity study of 4-dimethylaminoazobenzene in marmosets.

The marmoset, a small non-human primate, has rarely been used in toxicological studies. A short-term toxicity study was performed on common marmosets (BW = 330 +/- 32 g). Fifteen male marmosets received oral administration of DAB at a dose level of 56 mg/kg/day and 4 control animals received corn oil alone for a period of 15 days. Hematological, biochemical, histopathological and bone marrow examinations were carried out on the 5th, 10th and 15th day of treatment. Body weight decreased continuously and two animals died on day 10. Decreases in RBC, Hb and Ht and increases in MCV and WBC were observed. Uric acid and glucose were increased and AlP and LAP were decreased. Aldolase, GOT and GPT were increased by day 10, and thereafter recovery of aldolase to the control level and decreases of GOT and GPT were observed. Relative organ weights of the liver, kidney, spleen and adrenal were increased. Histologically, C-cell hyperplasia of the thyroid and slight changes of the liver were noted. Marrow total cell counts were not changed, but the G/E ratio was reduced. Thus, macrocytic anemia, an increase of marrow erythroblasts due to anemia and changes of biochemical parameters indicating liver injury were observed in marmosets; these findings were similar to those in rats in the previous experiments.

Administration, Oral