The effect of sonication on the particle size of lipopolysaccharide (LPS) in aqueous media was studied, in order to examine the relation of particle size to pyrogenicity in rabbits, by the sucrose density gradient ultracentrifugation technique. LPS extracted from E. coli UKT-B according to the phenol/water method showed a polydispersed profile on the gradients, but after sonication for 3 min it formed a single peak in the lower density regions. From the results of electron micrographic observations, partial specific volume, viscosity and turbidity measurements, and density gradient data, it was revealed that sonication produced a decrease in the particle size of LPS. A more marked pyrogenicity in rabbits was observed in the LPS fractions in the lower density regions than in the higher ones, or in the fractions having smaller-sized particles of LPS than in the fractions having larger particles.
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.
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.
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