The effects of neonatal vitamin A exposure on six behavioral parameters in adult Wistar rats were investigated. Newborn male rats were injected intraperitoneally with 80, 000 IU/kg/day of retinol palmitate (vitamin A) dissolved in physiological saline or vehicle alone (controls) during 1-5 days after birth. The animals were examined using the open field test (at 36 weeks of age), the rotarod test (38 weeks), the Biel water-maze test (40 weeks), the conditioned avoidance test (42 weeks), the running-wheel activity with pentobarbital challenge test (44 weeks), and the tail flick test (45 weeks). The vitamin A-exposed rats made significantly more errors and took significantly longer times in the Biel water-maze test, and showed significantly slower responses in the tail flick test than the controls. No significant effects of treatment with vitamin A were observed in any of the other behavioral tests. These results indicate that a long-lasting defect in learning in water-maze task and depression of the heat-pain response are induced in rats exposed neonatally to vitamin A.
Size-density fractionated coal fly ash particles, 1-5 μm in diameter and 2.4-2.8 g/cm3 in density, were administered to mouse lungs intratracheally. The change in the concentrations of metal elements in the lungs, kidneys, livers and spleens was measured by inductively coupled plasma atomic emission spectroscopy and atomic absorption spectroscopy up to 16 weeks after administration. In the lungs, each elemental concentration increased 1 week after administration and decreased thereafter with time after administration. For example, the concentrations of Al were 1018±272 μg/g tissue at 1 week and decreased thereafter to 556±177 μg/g tissue at 16 weeks after administration. The concentrations of Ca, Mn and Ni decreased more rapidly than the other elements, suggesting that Ca, Mn and Ni were dissociated from the alumino-silicate matrix of the fly ash particles in the lungs. In the kidneys, the concentration of Ni significantly increased at 2, 8 and 16 weeks after administration ; the concentration of Ni showed an increase of 0.4±0.2 μg/g over the control mouse at 16 weeks after administration. In the livers, increased concentrations of Ca and Mn were observed at 2, 4 and 16 weeks. On the other hand, no changes in the concentrations of these elements were observed in the spleen.
Toluene is a widely used solvent in industry which is the subject of abuse among the younger generation. A teratogenicity study of toluene by inhalation exposure was carried out in Sprague-Dawley rats and the effects on dams, fetuses and offspring were assessed. Pregnant females were exposed to 600 or 2000 ppm toluene for 6 h/day from day 7 to day 17 of pregnancy. The control group inhaled conditioned clean air under the same exposure conditions. Maternal exposure to 2000 ppm toluene caused significant toxic effects such as body weight suppression of dams and offspring, high fetal mortality and embryonic growth retardation, but no external, internal or skeletal anomalies were observed in the fetuses of any treated group. In addition, there were no differences in the results of pre- and postweaning behavioral tests of the offspring. However, no toxic or teratogenic changes which could be related to toluene exposure were apparent in the 600 ppm group. Further studies are warranted with toluene at higher concentrations applied during the period of organogenesis.
Alkaline ionized water (AKW) produced by electrolysis was given to gestational and lactational rats, and its effect on dams, growth of fetuses and offsprings were investigated. The results showed that the intake of food and water in dams increased significantly when AKW was given from the latter half of the gestation period and from the former half of the lactation period. Body weight of the offsprings in the test group, both males and females, increased significantly from the latter half of the lactation period. During the lactation period and after weaning, the offsprings in the test group showed significantly hastened appearance of abdominal hair, eruption of upper incisors, opening of eyelids and other postnatal morphological developments both in males and females, as well as earlier separation of auricle and descent of testes in males compared with the control was noted. As mentioned above, it was suggested from the observations conducted that the AKW has substantial biological effects on postnatal growth, since intake of food and water and body weight of the offsprings increased and postnatal morphological development was also accelerated.
The antidotal action of atropine sulfate and 2-pyridine aldoxime methiodide (2-PAM) against poisoning attributable to the new procarbamate insecticide benfuracarb [ethyl N-[2, 3-dihydro-2, 2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate] was compared utilizing rats as our experimental model. Both the intraperitoneal and oral administrations of these antidotes were examined after five, ten, fifteen and thirty minutes exposure periods, following treatment with benfuracarb at dose levels approximating LD50 and LD100. The results obtained demonstrate that both the intraperitoneal and oral administrations of atropine sulfate blocked or significantly reduced the toxic effects of benfuracarb and protected the animals from death. The intraperitoneal administration route appears to be more effective than was the oral route. In addition, the administration of atropine sulfate after the shorter period (up to 15 minutes), following exposure to benfuracarb, improved antidotal action, particularly with the LD100 dose of benfuracarb. It is suggested that atropine sulfate antagonizes benfuracarb poisoning by blocking acetylcholine (ACh) receptors, as many other carbamate insecticides, since benfuracarb was an in vivo cholinesterase (ChE) inhibitor and the toxic effect of benfuracarb was reduced by atropine sulfate. 2-PAM, however, did not significantly block or reduce the toxic effects of benfuracarb.
Radiosensitization of mice by dimethylbenzanthracene, diphenylcyclopropenone and aminoanthraquinones was investigated in a model where survival time after lethal radiation was scored. Survival time was shortened by nontoxic doses of the chemicals. The used in vivo system confirmed the radiosensitizing potential of dimethylbenzanthracene reported previously with in vitro studies. Moreover, radiosensitizing properties of diphenylcyclopropenone and aminoanthraquinones could be demonstrated. The sensitizing interaction of these chemicals with radiation adds a new facet to their toxicological spectrum and could, by enhancing radiation effects, influence estimates of risk. On the other hand, diphenylcyclopropenone or aminoanthraquinones deserve consideration as topical sensitizers in conditions where radiation is indicated to treat cutaneous malignancies.
Using 18-week-old and 52-week-old Wistar rats, we examined interleukin-6 (IL-6) production from osteoblasts and bone marrow macrophages treated with medroxyprogesterone acetate (MPA) and/or β -estradiol. The level of IL-6 production by osteoblasts was increased by treatment with MPA and, reversely, decreased by treatment with β-estradiol. These changes were especially remarkable in osteoblasts of 52-week-old rats. Additionally, and in contrast, the production of IL-6 by bone marrow macrophages was not significantly changed by treatment with both agents. These data suggest that because the increased production of IL-6 by osteoblasts treated with MPA in opposition with β-estradiol, MPA should be careful for osteoporosis dependent upon osteoclasts activated by IL-6. Finally, there was a marked difference in the amount of IL-6 produced between osteoblastd and bone marrow macrophages.
4-Nitrophenyl vinyl ether (NPVE) and phenyl vinyl ether (PVE) administered i.p. in mice lowered hepatic non-protein sulfhydryl (NP-SH) content, but did not elevate the serum glutamate pyruvate transaminase (GPT) activity. n-Butyl vinyl ether (BVE) showed no significant effects either on the NP-SH content or on the serum GPT activity. Mice pretreated with buthionine sulfoximine were sensitive to the potential toxicity of NPVE. These results showed that aryl vinyl ethers, NPVE and PVE, are more toxic than the alkyl vinyl ether, BVE, and that glutathione plays an important role on the protection of hepatic injury by reactive metabolite(s) derived from vinyl ethers.