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Biomedical subjects

T Itami

Publications and source records attributed to T Itami.

At least 37 records · Page 2Linked to original sources

Evaluation of the embryolethality of butyl benzyl phthalate by conventional and pair-feeding studies in rats.

The embryolethality of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at dosages of 0 (control) and 2.0% in the diet from day 0 to day 20 of pregnancy. Daily intake of BBP was 974 mg kg-1 for the 2.0% BBP group. In this group, all dams exhibited complete resorption of all the implanted embryos, and their food consumption, body weight gain and adjusted weight gain (body weight gain excluding the gravid uterus) during pregnancy were markedly lowered. To determine whether the embryolethality was the result of reduced food-consumption during pregnancy, a pair-feeding study was performed in which the pregnant rats received the same amount of diet consumed by the 2.0% BBP-treated pregnant rats. The pair-fed and 2.0% BBP-treated pregnant rats showed significant and comparable reductions in the adjusted weight gain. In the pair-fed group, the incidences of postimplantation and total losses were higher than those in the control group, and the number of live fetuses per litter was lower than the control value. However, the complete resorption of all the implanted embryos was not found in any of the pair-fed pregnant rats. It could be concluded that the embryolethality observed in the 2.0% BBP-treated pregnant rats is attributable to the effects of dietary BBP but not to the maternal malnutrition from reduced food consumption during pregnancy.

Animals↗

Teratogenicity of di-n-butyltin dichloride in rats.

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 0, 2.5, 5.0, 7.5 or 10.0 mg/kg on days 7-15 of pregnancy. Maternal toxicity occurred in the 7.5 and 10.0 mg/kg groups as evidenced by a significant increase in maternal death and decrease in food consumption and body weight gain. The incidence of fetuses with malformations was roughly proportional to the dose of DBT, and was significantly increased in the 5.0, 7.5 and 10.0 mg/kg groups. Cleft jaw, ankyloglossia, defects of the mandible, fusion of the ribs and deformity of the vertebral column were predominantly found. It is concluded that DBT produced teratogenic effects in the absence of maternal toxicity.

Abnormalities, Drug-Induced↗

Changes of spontaneous motor activity of rats after acute exposure to tributyltin chloride.

The effects of a single acute exposure to tributyltin chloride (TBTCl) on spontaneous motor activity (SMA) in home cage were studied in male Wistar rats. The rats were given TBTCl intraperitoneally at a dosage of 0, 1.6 or 3.3 mg/kg, and the SMA was measured for five days after administration of TBTCl. Body weight gain in the 3.3 mg/kg group was significantly lowered, but that in the 1.6 mg/kg group was comparable to that in the control group. The SMA during light phase was not affected by TBTCl treatment. However, the SMA during dark phase was decreased in both of the TBTCl-treated groups. These decreases in SMA gradually returned to the control levels. The 24-hr total daily and 12-hr nocturnal activity in the TBTCl-treated groups were decreased in a dose-dependent manner. These data indicate that TBTCl possesses behavioral toxicity and suggest that the decreased nocturnal SMA is a sensitive index for detecting toxicity of chemicals in rats.

Animals↗

Evaluation of the teratogenic potential of the plasticizer butyl benzyl phthalate in rats.

The teratogenicity of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at a dosage of 0, 0.25, 0.5, 1.0 or 2.0% in the diet from day 0 to day 20 of pregnancy. Daily intakes of BBP were 185 mg kg-1 for the 0.25% group, 375 mg kg-1 for the 0.5% group, 654 mg kg-1 for the 1.0% group and 974 mg kg-1 for the 2.0% group. Adjusted maternal body weight gain (body weight gain excluding the gravid uterus) during pregnancy in the 1.0 and 2.0% groups was significantly lowered. Food consumption during pregnancy in the 0.25 and 0.5% groups did not differ from that in the control group. No death was noted in the pregnant females of any group. There was no significant compound-related effects on the incidence of preimplantation loss. All dams given 2.0% BBP exhibited complete resorption of all the implanted embryos. Morphological examinations of the fetuses revealed no evidence of teratogenesis. It could be concluded that the no-observable-effect-levels (NOEL) in rats were 0.5 and 1.0% BBP in the diet for maternal and embryofetal toxicity, respectively.

Animals↗

Teratogenic evaluation of tributyltin chloride in rats following oral exposure.

The teratogenicity of tri-n-butyltin chloride (TBTC1) was examined in Wistar rats. The pregnant rats were administered orally 25, 15, 9, 5 and 0(Control) mg of TBTC1/kg of body weight/day from day 7 to 15 of pregnancy. Maternal toxicity, as evidenced by both of decreased body weight gain and food consumption was observed at 25, 15 and 9 mg/kg/day dose group. However, only in the 25 mg/kg/day dose group some clinical signs of toxicity (sedation, diarrhoea and salivation) were observed and 70 percent of the dams were dead. In the 25 mg/kg/day dose group, all fetuses were dead. Statistically significant reductions in the female fetal body weight were observed in 9 and 5 mg/kg/day dose groups. In all groups treated with TBTC1 except the 25 mg/kg/day dose group, no significant differences in the numbers of live fetuses and intrauterine death (dead fetuses and resorptions) or sex ratios of fetuses were found between the TBTC1-treated and control groups. Fetal external, skeletal and internal malformations were not observed at any of the dose levels. However, several types of skeletal and internal variations including delayed ossifications were observed in some groups treated with TBTC1, but the incidences were not significantly different from controls. Also, two fetuses with dilatation of the renal pelvis were found in 9 and 5 mg/kg/day dose group. Statistically significant increases of placental weight in all TBTC1-treated groups were observed when compared to that of control group. In conclusion, TBTC1 administered orally to Wistar rats during days 7-15 of pregnancy produced related signs of fetal toxicity but no evidence of teratogenicity and induced a marked increase in placental weight.

Abnormalities, Drug-Induced↗

[National Institute of Hygienic Sciences Standard (the Japanese Pharmacopoeia Standard) "Endotoxin Reference Standard" (Control 891)].

The second "Endotoxin Reference Standard" (Control 891) of the National Hygienic Sciences (Japanese Pharmacopoeia Standard) was prepared. As a result of the test of its potency against the preceding lot of the Reference Standard (Control 881), the second "Endotoxin Reference Standard" (Control 891) containing 16000 endotoxin units per vial was authorized.

Endotoxins↗

Evaluation of the teratogenic potential of the rubber accelerator N-cyclohexyl-2-benzothiazylsulfenamide in rats.

The teratogenicity of N-cyclohexyl-2-benzothiazylsulfenamide (CBS) was studied in Wistar rats. Pregnant rats were given CBS at a dosage of 0.001, 0.01, 0.1 or 0.5% in the diet from Day 0 to Day 20 of pregnancy. Daily intakes of CBS were 0.7 mg kg-1 for the 0.001% group, 7.1 mg kg-1 for the 0.01% group, 69.6 mg kg-1 for the 0.1% group and 288.8 mg kg-1 for the 0.5% group. Maternal body weight gain during pregnancy in the 0.1 and 0.5% groups was significantly lowered. Food consumption during pregnancy in the CBS-treated groups, except for the 0.5% group, did not differ from that in the control group. Neither death nor clinical signs of toxicity were noted in the pregnant females of any group. Lowered weight in fetuses and the placentae were observed in the 0.5% group. There were no significant compound-related effects on the incidences of pre- and post-implantation losses and the number and ratio of live fetuses. Morphological examinations of the fetuses revealed no evidence of teratogenesis. It could be concluded that CBS possesses no adverse effects on the prenatal development of the offspring in rats at doses employed in the present study.

Animals↗

Evaluation of teratogenic potential of sodium sulfite in rats.

The teratogenicity of sodium sulfite was examined in Wistar rats. The pregnant rats were fed diets containing 5, 2.5, 1.25, 0.63 or 0.32% of sodium sulfite heptahydrate(Na2SO3.7H2O) ad libitum from day 8 to 20 of pregnancy. Maternal toxicity, as evidenced by decreased body weight gain and decreased food consumption was observed at the 5% group, but no clinical signs of toxicity were observed. A significant reduction in the fetal body weight of both sexes was observed in all dose groups except 2.5% group. No significant differences in the numbers of live fetuses and intrauterine death (dead fetuses and resorptions) or sex ratios of fetuses were found between the sodium sulfite-treated and control groups. Fetal external, skeletal and internal malformations were not observed at any dose level. However, several types of skeletal and internal variations as well as delayed ossifications were observed in some groups treated with sodium sulfite, but the incidences were not significantly different from controls. Also, some fetuses with dilatation of the renal pelvis and the lateral ventricle were found in all groups except 1.25% group, but there was no dose-response. The live birth index and survival rate of offspring within 4 weeks and their body weight gain at 3 weeks after birth were not affected by sodium sulfite-treatment. In conclusion, sodium sulfite (0, 0.32, 0.63, 1.25, 2.5 or 5.0% as Na2SO3.7H2O) administered in the diet to Wistar rats during days 8-20 of pregnancy produced related signs of fetal toxicity but no evidence of teratogenicity.

Animals↗

Dolichol kinase in rat sarcoplasmic reticulum membrane preparations.

A dolichol kinase (EC 2.7.1.108) was found in sarcoplasmic reticulum membrane fractions from rat leg muscle. This enzyme specifically required CTP as a phosphoryl donor and relatively little activity was found in the absence of exogenous detergent-suspended dolichol. Unlike other reported dolichol kinases, the kinase from skeletal muscle was activated almost equally well by Ca2+, Zn2+, or Mg2+, but not Mn2+. No effect of calmodulin was seen. The kinase exhibited a single pH optimum at pH 7-8 in contrast to kinases from certain other tissues. Despite the low level of dolichol present in skeletal muscle, the kinase in the sarcoplasmic reticulum fraction had an activity comparable to that of microsomal preparations from tissues such as brain and liver, which may indicate that skeletal muscle has a high capacity for dolichol phosphorylation and protein glycosylation.

Animals↗

Teratology study of diethylene glycol mono-n-butyl ether in rats.

The teratogenicity of diethylene glycol mono-n-butyl ether (DEGMBE) was studied in Wistar rats. The pregnant rats were fed a diet containing DEGMBE from day 0 through day 20 of pregnancy. The dietary concentrations of DEGMBE were 0, 0.04, 0.2 and 1% and the daily intakes of DEGMBE were 0, 25, 115 and 633 mg/kg, respectively. In the DEGMBE-treated groups, the maternal body weight gain during pregnancy was significantly reduced, but neither decrease in food consumption during pregnancy nor any clinical sign of toxicity was observed. No significant differences between the DEGMBE-treated groups and the control group were found in the pre- and postimplantation losses, the number of live fetuses per litter, the sex ratio of live fetuses, the fetal body weight and the placental weight. External, skeletal and internal examinations of the fetuses revealed no evidence of teratogenesis. In the postnatal development of the offspring from the dams given DEGMBE, a high survival rate and good growth of the offspring were noted. It could be concluded that DEGMBE has no adverse effects on the pre- and postnatal development of the offspring in rats.

Animals↗

Teratology study of Tween 60 in rats.

The teratogenicity of Tween 60 was studied in Wistar rats. Pregnant rats were given Tween 60 at a dose of 0, 0.1, 1.0 or 10% in the diet from day 7 to day 14 of pregnancy. Daily intakes of Tween 60 were 99 mg/kg for the 0.1% group, 960 mg/kg for the 1.0% group and 7693 mg/kg for the 10% group. No change induced by Tween 60 was detected in the number, sex ratio and body weight of live fetuses. External, skeletal and internal examinations of the fetuses revealed no evidence of teratogenesis. It could be concluded that Tween 60 has no harmful effects on the prenatal development of the rat offspring at doses employed in the present study.

Animals↗

Malformations in rat fetuses induced by trypan blue.

Malformations of fetuses obtained from Wistar rat dams treated with trypan blue during gestation were studied. Fetuses were examined on day 20 of gestation. One hundred and twenty-seven fetuses showed abnormalities of the external features, skeleton and internal organs, separately or in combination. External malformations were found in 108 fetuses. The most frequent external malformation was anomaly of tail. Spina bifida, club foot, exencephaly and anal atresia were also observed frequently. Skeletal malformations were detected in 48 fetuses. Deformity of vertebrae in the lumbar, sacral and/or caudal regions was found in 46 fetuses. Internal malformations were observed in 27 fetuses. Anomaly of heart and/or great vessels, hydrocephaly and micro- or anophthalmia were observed frequently. About 90% of the fetuses with skeletal malformations also showed some external malformations. In contrast, about 48% of the fetuses with internal malformations also had some external malformations. These results suggest that, for teratological study, internal examination is more important in detecting malformations of fetuses than skeletal examination.

Abnormalities, Drug-Induced↗

[A cylindrical thermistor probe for experiments on suppositories in rabbits].

A cylindrical thermistor probe with a rubber disk stopper, which is beneficial for inserting a suppository into the rectum of rabbits without removal of the probe from the rectum, was developed. It is possible to measure body temperature continuously by using this probe in an experiment to assess the effects of a suppository on the body temperature of rabbits. After insertion of a suppository, leakage of the melted suppository from the rectum was not observed. No differences between this thermistor probe and an ordinary thermistor probe in the ability of the probe to detect the febrile response of rabbits injected with a bacterial pyrogen were observed. From these results, it could be concluded that this newly improved cylindrical thermistor probe is suitable for studying the effect of suppositories on the body temperature of rabbits.

Animals↗

Antipyretic effect of indomethacin suppository in rabbits.

We have designed a thermistor rectal probe thermometer for measuring the antipyretic activity of suppositories. Using this thermistor probe, we tested the antipyretic effect of an indomethacin suppository in comparison with oral and intravenous administrations in rabbits (male, 2.5-2.9 kg). The rectal temperature of normal rabbits remained unchanged after rectal and intravenous administration of indomethacin, 25 mg/body and 10 mg/kg, respectively. The antipyretic effect was tested in febrile rabbits injected with bacterial pyrogen, lipopolysaccharide (LPS) 0.2 microgram/kg (i.v.). The dose-dependent antipyretic activities were observed in febrile rabbits administered with indomethacin by rectal (6.3-23.7 mg/body), intravenous (2.5-10 mg/kg) and oral (2.5-20 mg/kg) routes. When indomethacin was administered simultaneously or 1 h after LPS, the most potent antipyretic effect was observed in the case of rectal administration and the weakest effect was observed in that of oral administration. These data indicate that the rectal administration of drugs can produce a potent antipyretic activity, not inferior to that of the intravenous injection.

Administration, Oral↗

Antipyretic mechanism of indomethacin in rabbits.

The mechanism of the antipyretic effect of indomethacin (IM) on fever induced by bacterial pyrogen (LPS, 0.2 microgram/kg, i.v.), leukocytic pyrogen (LP, 2 ml/kg, i.v.) and 2,4-dinitrophenol (DNP, 20 mg/kg, i.m.) in male adult rabbits was studied. In plasma, the biological half lives of IM in normal and LPS-injected rabbits were estimated to be 24 and 21 min in the early phase and 72 and 51 min in the late phase, respectively. A potent antipyretic effect was observed with intravenous injection of IM in LPS- and LP-induced fevers, but not in DNP-induced fever. The antipyretic effect was also observed with intracisternal injection of indomethacin at doses of 0.025 and 0.013 mg/kg. The activity of endogenous pyrogen in serum after LPS injection was not suppressed by the injection of IM (10 mg/kg, i.v.). The production of LP by leukocytes in vitro was not inhibited by IM (10 micrograms/ml). In our previous report, it was ascertained that the rectal temperature of normal rabbits remained unchanged after intravenous injection of IM. These results suggest that indomethacin may inhibit only the pyretic processes in the central nervous system.

2,4-Dinitrophenol↗

[Thermistor probe for testing an antipyretic suppository in rabbits].

The thermistor probe for estimating the effects of an antipyretic suppository after its administration into the rectum of the rabbit was studied. A thermistor probe with three rubber disk stoppers was confirmed to be able to prevent the leakage of drugs from the rectum of a rabbit restrained in a neck stock. By using this newly devised thermistor probe or the usual thermistor probe without a stopper, the febrile response was determined in rabbits injected with bacterial pyrogen. There was no difference in the ability to detect rectal temperature between the two thermistor probes. From these results, it could be concluded that this newly devised thermistor prove was useful in studying the effects of antipyretic suppositories in rabbits.

Animals↗