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Biomedical subjects

M Ema

Publications and source records attributed to M Ema.

At least 19 recordsLinked to original sources

cDNA cloning and structure of mouse putative Ah receptor.

Mouse cDNA clones for a putative Ah receptor have been isolated from a cDNA library of mRNA from Hepa-1 cells by an oligonucleotide probe produced by PCR with a pair of primers which was synthesized according to the reported N-terminal sequence of 26 amino acids. The cDNA clones encode a polypeptide of 805 amino acids with a helix-loop-helix motif and with some similarity to a certain region designated PAS of Drosophila Per and Sim, and human Arnt protein. Cotransfection of an expression vector of the Ah receptor with a reporter plasmid pMC6.3k consisting of CYP1A1 promoter and CAT structural gene into CV-1 cells enhanced the CAT expression in response to added 3-methylcholanthrene.

Amino Acid Sequence

Effect of period of exposure on the developmental toxicity of butyl benzyl phthalate in rats.

The objective of the present study was to determine if periods of exposure would modify the developmental toxicity of butyl benzyl phthalate (BBP). Pregnant Wistar rats were given BBP at a dose of 2.0% in the diet on days 0-20, days 0-7, days 7-16 or days 16-20 of pregnancy. Food consumption and body weight gain were decreased in the pregnant rats given BBP. All dams given BBP on days 0-20 exhibited complete resorption of all the implanted embryos. Post-implantation loss in the pregnant rats given BBP on days 0-7 or 7-16 was higher than that in the control and pair-fed pregnant rats. No increase in post-implantation loss was found in the pregnant rats given BBP on days 16-20. Pre-implantation loss in the BBP-treated groups was comparable to the control and pair-fed groups. Striking teratogenicity was detected in fetuses of the dams given BBP on days 7-16. Cleft palate and fusion of the sternebrae were predominantly observed. About 95% of the fetuses in this group had cleft palate. The incidence of malformations in this group was significantly and markedly higher than that in the control and pair-fed groups.

Abnormalities, Drug-Induced

Embryolethality and teratogenicity of butyl benzyl phthalate in rats.

Pregnant Wistar rats were given butyl benzyl phthalate (BBP) at a dose of 2.0% in the diet on days 0-20, days 0-11 or days 11-20 of pregnancy. Food consumption and body weight gain were decreased in pregnant rats given BBP. Pre-implantation loss in the BBP-treated groups was comparable to that in the control and pair-fed groups. All dams given BBP on days 0-20 or days 0-11 exhibited complete resorption of all the implanted embryos. No increase in post-implantation loss was found in pregnant rats given BBP on days 11-20. Marked teratogenicity was detected in fetuses of the dams given BBP on days 11-20. Cleft palate and fusion of the sternebrae were predominantly observed. Seventy-two of the 134 fetuses had a cleft palate. The incidence of malformations in this group was significantly and markedly higher than that in the control and pair-fed groups. In conclusion, the administration of BBP during the first and second half of pregnancy produced embryolethality and teratogenicity, respectively.

Abnormalities, Drug-Induced

Susceptible period for the teratogenicity of di-n-butyltin dichloride in rats.

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 20 mg/kg on days 7-9, 10-12 or 13-15 of pregnancy or at a dose of 20 or 40 mg/kg on day 6, 7, 8 or 9 of pregnancy. While treatment with DBT on days 7-9 was significantly and highly teratogenic, no evidence of teratogenicity was detected when DBT was given on days 10-12 or 13-15. Treatment on day 7 or 8 with both doses of DBT, but neither on day 6 or 9, resulted in an increased incidence of fetuses with malformations. The highest incidence of malformed fetuses occurred after treatment on day 8. The incidence of malformed fetuses was proportional to the dose of DBT. Anomaly of tail, anal atresia, club foot, omphalocele, deformity of the vertebral column, defect of the ribs and anophthalmia or microphthalmia were predominantly observed. It could be concluded that, following maternal exposure to DBT in rats, developing offspring are not susceptible to teratogenic effects of DBT on day 6 and that day 7 is the earliest susceptible period, day 8 is the highest susceptible period and day 9 is no longer a susceptible period for teratogenesis of DBT.

Animals

Teratological assessment of glutaraldehyde in rats by gastric intubation.

Pregnant rats were given glutaraldehyde (GA) by gastric intubation at a dose of 0, 25, 50 or 100 mg/kg on days 6-15 of pregnancy. Maternal toxicity occurred in the 100 mg/kg group as evidenced by a significant increase in maternal death and a significant decrease in maternal body weight gain and food consumption. A significantly lowered fetal weight was also found in the 100 mg/kg group. No significant change induced by GA was detected in the incidence of postimplantation loss. Morphologic examinations of fetuses revealed no evidence of teratogenicity of GA. It could be concluded that GA has no teratogenic effects on rat offspring even at a dose which induced severe maternal toxicity.

Abnormalities, Drug-Induced

Teratogenic evaluation of butyl benzyl phthalate in rats by gastric intubation.

Pregnant rats were given butyl benzyl phthalate (BBP) by gastric intubation at a dose of 0, 0.5, 0.75 or 1.0 g/kg on days 7-15 of pregnancy. In the 0.5 g/kg group, food consumption during the administration period was significantly decreased, but no adverse effect on the embryo-fetus was detected. High maternal lethality and complete resorption of implanted embryos in all the surviving dams were observed in the 1.0 g/kg group. Increased embryo-fetal death and decreased fetal weight were found at a dose of 0.75 g/kg which also caused reductions in maternal body weight gain and food consumption. A significantly and markedly increased incidence of fetal malformations was also detected in the 0.75 g/kg group. Cleft palate, fusion of the sternebrae and dilatation of the renal pelvis were mostly observed.

Abnormalities, Drug-Induced

Teratological assessment of diiodomethyl p-tolyl sulfone in rats.

Pregnant rats were given diiodomethyl p-tolyl sulfone (DIMPTS) at a dose of 0, 0.125, 0.25, 0.5 or 1.0% in the diet on days 6-15 of pregnancy. Maternal body weight gain and food consumption during the administration period were significantly lowered in the 0.25, 0.5 and 1.0% groups. No significant changes induced by DIMPTS were detected in the number of resorptions and dead fetuses, and body weight of live fetuses. Morphological examinations of fetuses revealed no evidence of teratogenesis. It could be concluded that DIMPTS has no teratogenic effects on rat offspring, even at doses which induced maternal toxicity.

Abnormalities, Drug-Induced

[Antipyretic effects of traditional Chinese medicines in bacterial endotoxin-induced febrile rabbits].

The antipyretic effects of oral administration of eight traditional Chinese medicines (dried extracts) were tested in febrile rabbits injected with bacterial pyrogen, lipopolysaccharide (LPS) 0.05 micrograms/kg (i.v.). The traditional Chinese medicines were given 0.6-2 g/10 ml/kg (p.o.) simultaneously with LPS. The most potent antipyretic effect was observed in Dai-jyoki-to (Ta-chen-chi-tang). The moderate antipyretic effects were observed in Toki-syakuyaku-san (Tang-kuei-shao-yao-san) and Syo-saiko-to (Hssiao-chai-hu-tang). Koso-san (Hsiang-su-san), Oren-gedoku-to (Huang-lien-chieh-tu-tan), Gorei-san (Wu-ling-san), Kakkon-to (Ko-ken-tang) and Byakkoka-ninjin-to (Pai-hu-chia-jen-sheng-tang) showed no effects.

Animals

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 the teratogenic potential of the rubber accelerator dibenzthiazyl disulphide in rats.

The teratogenic potential of dibenzthiazyl disulphide (MBTS) was studied in Wistar rats. Pregnant rats were given MBTS at a dosage of 0, 0.04, 0.2 or 1% in the diet from day 0 to day 20 of pregnancy. Daily intakes of MBTS were 26 mg kg-1 for the 0.04% group, 127 mg kg-1 for the 0.2% group and 596 mg kg-1 for the 1% group. Maternal body weight gain during day 0 to day 14 of pregnancy in the 1% group was significantly lowered, but no significant changes induced by MBTS were observed in any other maternal parameters, such as food consumption and clinical sign of toxicity. There were no significant compound-related effects on the incidences of pre- and postimplantation losses and the number, sex ratio and body weight of live fetuses. Morphological examinations of the fetuses revealed no evidence of teratogenesis. In the postnatal development of the offspring from the dams given MBTS, a high survival rate and good growth of the offspring were seen. It could be concluded that MBTS possesses no adverse effects on the pre- and postnatal development of the offspring in rats at the 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

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