摄入氯化铝后大鼠某些器官内铝含量的变化

用原子吸收分光光度计测定摄入含铝饲料和饮水的大鼠大脑、小脑、肾、肝和骨的铝含量变化。发现染铝14天后,各器官铝含量显著上升;25天后仅骨铝含量明显增高;40天后肝和骨铝含量亦上升明显。停止染铝8天后,各器官铝含量均未降至正常,且小脑及骨铝含量仍有轻微上升。表明摄入铝后,铝可在体内蓄积,尤其是小脑和骨。     

Transient renal impairment in rats after oral exposure to diethylene glycol

Volume, specific gravity, creatinine, lactate dehydrogenase (LDH), leucine aminopeptidase (LAP), beta-galactosidase (GAL), leucocytes, erythrocytes, nitrite, protein (albumin), glucose, ketone, urobilinogen, bilirubin and pH were estimated in urine of rats after single (by gavage) or repeated (via drinking water) oral administration of diethylene glycol (DEG). Following single or repetitive doses (daily over 90 days) of 0.2 g DEG kg-1 body weight, no change in renal function was observed (no effect level). In urine of rats treated once with 0.7 g DEG kg-1 body weight, LDH activity was significantly enhanced one day after treatment. A single dose of 2.0 g DEG kg-1 body weight resulted in an additional rise in urinary GAL activity two days after treatment, a significant rise of urinary volume and a decrease in creatinine concentration and pH on the first day. One day following a single dose of 8.0 g DEG kg-1 body weight, in addition to the changes mentioned before, LAP activity was significantly elevated and the specific gravity decreased. However, in all experiments the wet weight of the kidneys remained normal as compared to controls. The results thus show dose-dependent changes in several renal parameters, indicating a slight-to-moderate and reversible renal impairment.     

孕鼠染铝对胎鼠脑皮质神经元的影响

目的探讨母体孕期染铝对胚胎脑神经发育的毒性作用。方法 4-5月龄SD大鼠,雌雄各30只,1：1合笼喂养,每天早晨查雌鼠阴栓,发现阴栓即进入实验（E0）,将孕鼠随机平分为2组。染铝组：E0-E18期间以AlCl3100mg/（kg.d）灌胃,正常对照组：以等量蒸馏水灌胃。取孕鼠18d胚胎,每只孕鼠任取其胚胎2只,每小组子代30只。常规石蜡切片,经神经元特异烯醇酶（Neuron specific enolase,NSE）免疫组化染色。分别对胎鼠皮质Par1区内椎体细胞层NSE免疫组化染色阳性反应细胞进行计数,并用细胞形态学计量方法测量阳性反应产物的平均光密度。结果染铝组胎鼠NSE免疫组化染色阳性细胞均明显少于对照组胎鼠（P〈0.05）,阳性反应产物平均光密度均低于对照组胎鼠（P〈0.05）。结论大鼠孕期染铝可导致胎鼠脑神经元数量减少,从而导致子代鼠神经发育障碍。     

Cardiotoxicity and hypertension in rats after oral lead exposure

The rats were exposed to lead (0.25, 0.5 and 1.0 per cent lead acetate through drinking water) for 90 days to study its effect on some physiological and morphological parameters of the cardiovascular system. Blood lead levels increased in a dose dependent manner but heart tissue showed rise at only two higher doses in exposed animals. The two higher doses of lead resulted in an increased arterial blood pressure and calcium influx in atrial trabeculae and papillary muscles. No marked pathological or histochemical changes were observed in heart tissue excepting congestion and slightly reduced activity of succinic dehydrogenase in the highest dosed group. It was concluded that lead exposure through drinking water may produce increased arterial blood pressure and minor changes in the myocardium. Whether these changes are mediated through the effect of lead on the calcium transport needs further investigation.     

Encephalopathy in rats and nephropathy in rats and mice after subchronic oral exposure to benzaldehyde

Male and female Fischer 344 rats and B6C3F1 mice were treated daily (5 days/wk) with benzaldehyde by gavage either in 12 doses of 0 (vehicle control), 100 (rats only), 200, 400, 800, 1600 or (for mice only) 3200 mg/kg body weight/day (followed by 2 days' observation without treatment), or for 90 days in doses of 0, 50, 100, 200, 400 or 800 mg/kg/day (rats) or 0, 75, 150, 300, 600 or 1200 mg/kg/day (mice). In the acute studies, benzaldehyde induced deaths and decreased body-weight gain in both sexes of rats given 800 or 1600 mg/kg/day and caused deaths in both sexes of mice given 1600 or 3200 mg/kg/day. In the 90-day studies, deaths occurred in both sexes of rats on 800 mg/kg/day and in male mice on 1200 mg/kg/day. Body-weight gain was depressed in male rats on 800 mg/kg/day, in male mice on 600 mg/kg/day and in female mice on 1200 mg/kg/day. Necrotic and degenerative lesions were seen in the cerebellar and hippocampal regions of the brain in both sexes of rats given 800 mg/kg/day, but not in mice. Renal tubular necrosis occurred in male and female rats on 800 mg/kg/day and in male mice on 1200 mg/kg/day. Mild epithelial hyperplasia or hyperkeratosis of the forestomach was seen in male and female rats on 800 mg/kg/day. In this limited study, the no-observed-toxic-effect doses of benzaldehyde administered by gavage were 400 mg/kg/day in male and female rats, 300 mg/kg/day in male mice and 600-1200 mg/kg/day in female mice.     

Toluene concentrations in various tissues of rats after inhalation and oral administration

The uptake, distribution, and elimination of ³H-toluene in various tissues of rats were studied after inhalation or after gastric intubation.The maximum radioactivity was measured 2–3 h after gastric intubation in tissues, except in white adipose tissue, where the peak radioactivity was reached at 5 h.After inhalation exposure, the uptake to various tissues was very rapid. The maximum radioactivity in most tissues was reached in 15–30 min. The accumulation was slowest in white adipose tissue, where it took 1–2 h.The radioactivity in tissues decreased after inhalation exposure more rapidly than after gastric intubation. Brown adipose tissue and white adipose tissue were different from other tissues in their ability to retain toluene. Twenty-four hours after exposures, only 1% or less of the initial radioactivity was found in tissues other than white adipose tissue, in which the corresponding value was 3.5–5%.The results show a very rapid absorption and distribution of toluene after inhalation and a retention of radioactivity in white adipose tissue. After oral ingestion the distribution showed a similar but much slower pattern.

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Zusammenfassung Nach Inhalation und nach oraler Gabe wurden Aufnahme, Verteilung und Ausscheidung von ³H-Toluol in verschiedenen Geweben der Ratte untersucht.Bei oraler Gabe (mittels Schlundsonde) wurde das Maximum an Radioaktivität im weißen Fettgewebe nach 5 Std erreicht, während es in allen anderen untersuchten Organen bereits nach 2–3 Std auftrat. Nach Inhalation wurde ³H-Toluol wesentlich schneller aufgenommen. Die höchste Radioaktivität wurde hierbei im weißen Fett nach 1–2 Std und in den meisten anderen Geweben nach 15–30 min gemessen. Ebenso war die Abnahme der Radioaktivität nach Inhalation schneller als nach oraler Gabe, wobei sich auch in diesem Fall das braune und das weiße Fettgewebe von anderen Organen unterschieden. Vierundzwanzig Stunden nach Applikation enthielt das Fett noch 3,5–5% der initialen Radioaktivität, während in allen anderen Geweben nur noch 1% oder weniger gemessen wurden.Die Ergebnisse dieser Studie zeigen, daß Toluol nach Inhalation sehr viel rascher absorbiert und wieder ausgeschieden wird, als nach oraler Aufnahme, während das Verteilungsmuster nach beiden Applikationsarten sehr ähnlich ist.

     

Inhalation toxicity of acetaldehyde in rats. IV. Progression and regression of nasal lesions after discontinuation of exposure

As part of a long-term inhalation toxicity study with acetaldehyde in rats, progression and regression of nasal lesions were studied in animals exposed to 0, 750, 1500 and 3000/1500 ppm of the test compound for 52 weeks and killed after recovery periods of 26 or 52 weeks. Major compound-related nasal lesions found at the end of the exposure period comprised: (a) thinning of the olfactory epithelium with loss of sensory and sustentacular cells at all concentrations; this condition was accompanied by focal basal cell hyperplasia in low- and mid-concentration animals; (b) hyper- and metaplasia of the respiratory epithelium frequently accompanied by keratinisation and occasionally by proliferations of atypical basal cells in the top-concentration group; and (c) rhinitis in several top-concentration rats. There was strong evidence on the one hand that the hyper- and metaplastic changes found in the respiratory epithelium and the basal cell hyperplasia seen in the olfactory epithelium after 52 weeks of exposure may progress to neoplasms despite discontinuation of the treatment. On the other hand these hyper- and metaplastic changes may regress during the recovery period. Regeneration of the olfactory epithelium was evident in several low- and mid-concentration animals, but not in top-concentration rats. The regenerated epithelium was seen as a layer of stratified undifferentiated epithelium containing small nerve bundles, tiny groups of sensory cells, and groups of epithelial cells resembling acinar cells of the glands of Bowman. Furthermore, replacement of olfactory epithelium by respiratory epithelium was a frequent finding. It was concluded that rat olfactory epithelium severely damaged by acetaldehyde may regenerate, most probably from basal cells, provided the olfactory epithelium has not been fully destroyed.     

Urinary excretion of ethylenethiourea and kidney morphology in rats after continuous oral exposure to nabam or ethylenethiourea

Nabam, an ethylenebisdithiocarbamate (EBDC), is an agricultural fungicide. Ethylenethiourea (ETU), widely used in the rubber industry, is a degradation and byproduct of metabolism and of storage and production of EBDCs. Kidney function and morphology, and urinary excretion of ETU, were studied in rats exposed to nabam or ETU in drinking water for 28 days. The concentrations of nabam in drinking water were 0, 50, 100 or 200 mg/l, and of ETU 0, 100, 200 or 300 mg/l. Both compounds decreased body weight gain but did not significantly affect urinary sodium, potassium, glucose, or protein excretion, or urinary osmolality. Urinary vasopressin was also unaltered after exposure to nabam or ETU. High doses of ETU resulted in ultrastructural alterations in epithelial cells of renal proximal tubuli. ETU was excreted in urine after exposure to both nabam and ETU. There seemed to be a threshold dose of ETU below which no ultrastructural alterations in kidney occurred.     

Effects of oral exposure to silver nanoparticles on the sperm of rats

It has been demonstrated that exposure to silver nanoparticles (AgNPs) can induce toxicological effects in rodents. In this study, we investigated whether sub-chronic oral exposure to different doses of polyvinil pyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) (50, 100 and 200 mg/kg/day) could induce harmful effects on epididymal sperm rat parameters. Sperm motility, viability and morphology were examined. Moreover, a histological evaluation of testis and epididymis was also performed. High doses of PVP-AgNPs showed higher sperm morphology abnormalities, while a progressive, but not significant effect, was observed in other sperm parameters. The current results suggest that oral sub-chronic exposure to PVP-AgNPs induces slight toxicological effects in sperm rat parameters.     

Examination of new bone growth on aluminium oxide implant contact surfaces after oral administration of ossein-hydroxyapatite compound to rats

In view of the many disadvantages of transplantation of autologous bone tissue, factors must be found which locally and systemically will adjust the balance between bone resorption and deposition in favour of new bone growth. The present study was undertaken, therefore, to examine whether oral administration of ossein-hydroxyapatite compound (OHC) could stimulate new bone growth on aluminium oxide implant surfaces and, if so, whether it was the mineral or organic part of the compound which was responsible. Whilst under anaesthesia, adult male Wistar rats each had 2 holes drilled into the femur and 2 precisely fitting aluminium oxide implants inserted. The animals were divided into 5 groups each of 5 rats and the groups received oral daily doses of 20 mg OHC, 100 mg OHC, 10 mg hydroxyapatite, 50 mg hydroxyapatite or no supplement (controls), respectively. After 20 days, each implant was evaluated by 5 cuts through the marrow area and the thickness of the newly grown layer of bone measured by a morphometric procedure. The results showed a significant increase in new bone growth for the 100 mg OHC group in comparison to the control group, and in comparison to the hydroxyapatite group. Because both supplemented groups received equivalent dosages of calcium and phosphate, the additional stimulation of new bone growth must have been due to the organic part of OHC (ossein). It is suggested that these results should stimulate in particular the clinical use of OHC in the critical initial phase of implant healing and delayed fracture healing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inorganic and organic fluoride concentrations in tissues after the oral administration of sodium monofluoroacetate (Compound 1080) to rats

Male rats were used to study the inorganic (ionic) and organic fluoride concentrations in plasma, liver, kidneys and stomach content after oral doses of 0, 2.2, 3.5, 4.0, 5.0 and 7.0 mg sodium monofluoroacetate (SMFA, Compound 1080)/kg body weight. Tissue and plasma ionic fluoride concentrations were observed to be higher in all rats given SMFA as compared to rats in the control group. This observation suggests in vivo defluorination of SMFA. Homogenates of liver obtained from SMFA poisoned rats showed significant increases in ionic fluoride concentration during a 6-day storage period at +4 degrees C, with the total fluoride concentration (ionic and organic) remaining constant. The average percentages of distribution of SMFA (organic fluoride) in plasma, liver, and kidneys were 7.05, 5.07 and 1.68, respectively. Plasma and tissue SMFA concentrations were generally lower than the corresponding stomach fluid SMFA concentrations for all dosage groups. Lethal concentration of SMFA in the liquid stomach content was in the range 84.9--189 micrograms/ml, corresponding to total (ionic and organic) fluoride concentrations in the range of 16.1--36 micrograms/ml.     

Effect of oral and inhalation exposure to cadmium on the oestrous cycle in rats

Female rats were administered by gavage an aqueous solution of CdCl2 for 14 weeks, 5 days per week, at doses of 0.04, 0.4, 4 and 40 mg Cd/kg/day or exposed by inhalation to CdO for 20 weeks (5 h per days, 5 days per week) at concentrations of 0.02, 0.16 and 1 mg Cd/m3. A pronounced increase in the mean duration of the oestrous cycle mainly due to lengthening of dioestrus was noted already 6 weeks after treatment of females given per os 40 mg Cd/kg or exposed to a concentration of 1 mg Cd/m3. No changes in the mean duration of the oestrous cycle were found in other experimental groups, although in the 0.16 mg Cd/m3 group an increased percentage of females with oestrous cycles lasting over 6 days was shown 18 weeks after exposure. Since Cd-induced lethality and decrease in body weight gain were observed in females given by gavage 40 mg Cd/kg or exposed by inhalation to a concentration of 1 mg Cd/m3, it is concluded that exposure to cadmium does not affect the sexual cycle unless other overt signs of Cd-toxicity are induced.     

Pregnancy outcome after exposure to oral contraceptives during the periconceptional period

To evaluate whether periconceptional exposure to oral contraceptives (OCs) increased adverse pregnancy outcomes, 136 pregnant women taking OCs within the periconceptional period were identified at the Korean Motherisk Program. Of them, 120 pregnant women accepted to participate in their study and were followed up until completion of the pregnancy. A control group of 240 age- and gravidity-matched pregnant women exposed to non-teratogen drugs for at least 1 month before pregnancy was also included. The median gestational age at delivery was 39.1 (27.0-41.0) weeks in the exposed group and 39.3 (27.4-42.0) weeks in the control group (P = 0.19). In the exposed group, 7.1% of babies were born with low birth weight versus 2.6% in the control group (P = 0.068). The number of preterm deliveries or babies born large for gestational age did not differ between the two groups. In the exposed group, the rate of birth defects was 3.2% (n = 3/99) versus 3.6% (n = 7/193) in the control group (P = 1.0). There were 15 women who took high doses of progesterone (emergency contraception) and no adverse fetal outcomes were observed. In conclusion, periconceptional exposure to OCs does not appear to increase the risk for adverse pregnancy outcomes.     

Elevation in metallothionein messenger RNA in rat tissues after exposure to X-irradiation

Metallothionein (MT) mRNA levels in tissues were measured in rats following whole-body X-irradiation (2 and 20 Gy). When compared with control rats, the elevation in MT mRNA levels of liver, kidney, and thymus was observed in irradiated rats at 9 or 72 hr after irradiation. However, the elevation in MT mRNA levels was not observed in brain, spleen, lung, heart, and testis. When compared with other tissues, testicular MT mRNA levels in control rats were extremely high, and treatment with X-irradiation produced a slight decrease of testicular MT mRNA levels. Time-course experiments indicated that hepatic and renal MT mRNA reached a maximum at 6 hr after irradiation. In low-dose (2 Gy) irradiated rat, these values were returned to control values by 4 days after irradiation. However, in high-dose (20 Gy) irradiated rat, the values were not decreased to control values. These data indicate that treatment with X-irradiation produces an elevation in MT mRNA in rat tissues.     

Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats

Copper oxide (CuO) nanoparticles (NPs) and copper carbonate nanoparticles (Cu₂CO₃(OH)₂ NPs have applications as antimicrobial agents and wood preservatives: an application that may lead to oral ingestion via hand to mouth transfer. Rats were exposed by oral gavage to CuO NPs and Cu₂CO₃(OH)₂ NPs for five consecutive days with doses from 1 to 512?mg/kg and 4 to 128?mg/kg per day, respectively, and toxicity was evaluated at days 6 and 26. Both CuO NPs and Cu₂CO₃(OH)₂ NPs induced changes in hematology parameters, as well as clinical chemistry markers (e.g. increased alanine aminotransferase, ALT) indicative of liver damage For CuO NPs histopathological alterations were observed in bone marrow, stomach and liver mainly consisting of an inflammatory response, ulceration, and degeneration. Cu₂CO₃(OH)₂ NPs induced morphological alterations in the stomach, liver, intestines, spleen, thymus, kidneys, and bone marrow. In spleen and thymus lymphoid, depletion was noted that warrants further immunotoxicological evaluation. The NPs showed partial dissolution in artificial simulated stomach fluids, while in intestinal conditions, the primary particles simultaneously shrank and agglomerated into large structures. This means that both copper ions and the particulate nanoforms should be considered as potential causal agents for the observed toxicity. For risk assessment, the lowest bench mark dose (BMD) was similar for both NPs for the serum liver enzyme AST (an indication of liver toxicity), being 26.2?mg/kg for CuO NPs and 30.8?mg/kg for Cu₂CO₃(OH)₂ NPs. This was surprising since the histopathology evidence demonstrates more severe organ damage for Cu₂CO₃(OH)₂ NPs than for CuO NPs.     

Tin distribution in adult rat tissues after exposure to trimethyltin and triethyltin

The time course of distribution of tin in the adult rat was determined in brain, liver, kidneys, heart, and blood following single ip administrations of trimethyltin hydroxide (TMT) and triethyltin bromide (TET). Adult Long-Evans rats were killed 1, 4, 12, and 24 hr, and at 5, 10, or 22 days following injection of TMT and TET (N = 6/time), and tissues were analyzed for total tin by atomic absorbance spectroscopy. TET exposure resulted in higher tin concentrations in brain, liver, and kidney tissues, while the two trialkyltins resulted in approximately equal tin concentrations in the heart and blood. Rates of elimination of tin (expressed as elimination rate constants, Kel) were greater in all tissues following TET exposure than following TMT exposure. The concentration of tin in the brain 12 hr after TMT exposure was 4.4, 8.5, and 12.7 ng tin/mg protein for dosages of 3.0, 6.0, and 9.0 mg/kg, respectively. Tin was evenly distributed across the cerebellum, medulla-pons, hypothalamus, hippocampus, and striatum following TMT exposure. These results describe major differences in the disposition and rates of elimination of tin from body tissues after TMT and TET exposure, and demonstrate that the regional disposition of tin is not related to the region-specific pathology reported following TMT exposure.     

Arsenicals in maternal and fetal mouse tissues after gestational exposure to arsenite

Exposure of pregnant C3H/HeNCR mice to 42.5- or 85-ppm of arsenic as sodium arsenite in drinking water between days 8 and 18 of gestation markedly increases tumor incidence in their offspring. In the work reported here, distribution of inorganic arsenic and its metabolites, methyl arsenic and dimethyl arsenic, were determined in maternal and fetal tissues collected on gestational day 18 of these exposure regimens. Tissues were collected from three females and from associated fetuses exposed to each dosage level. Concentrations of total speciated arsenic (sum of inorganic, methyl, and dimethyl arsenic) were higher in maternal tissues than in placenta and fetal tissues; total speciated arsenic concentration in placenta exceeded those in fetal tissues. Significant dosage-dependent (42.5 ppm versus 85 ppm of arsenite in drinking water) differences were found in total speciated arsenic concentrations in maternal lung (p<0.01) and liver (p<0.001). Total speciated arsenic concentrations did not differ significantly between dosage levels for maternal blood or for fetal lung, liver, and blood, or for placenta. Percentages of inorganic, methyl, or dimethyl arsenic in maternal or fetal tissues were not dosage-dependent. Over the range of total speciated arsenic concentrations in most maternal and fetal tissues, dimethyl arsenic was the most abundant arsenical. However, in maternal liver at the highest total speciated arsenic concentration, inorganic arsenic was the most abundant arsenical, suggesting that a high tissue burden of arsenic affected formation or retention of methylated species in this organ. Tissue concentration-dependent processes could affect kinetics of transfer of inorganic arsenic or its metabolites from mother to fetus.     

Caffeine disposition after oral administration to pregnant rats

1. Caffeine disposition was studied over 24?h in rats on the 12th day of pregnancy given 80?mg/kg of drug as a single oral dose or in four divided doses every three hours.

2. Peak blood levels of caffeine were reached at three hours after the single dose, and at 10?h (at half the previous value) after the first of the divided doses.

3. At the end of the experiment both caffeine and its dimethylxanthine metabolites were higher in blood, amniotic fluid and fetuses after divided doses than after the single dose. Urinary excretion over 24?h was the same for the two groups.

4. The overall conclusions underline that caffeine per se and not its metabolites are responsible for the teratogenic effects.     

MicroRNA response of inhalation exposure to hexanal in lung tissues from Fischer 344 rats

In previous studies, we have investigated the relationships between environmental chemicals and health risk based on omics analysis and identified significant biomarkers. Our current findings indicate that hexanal may be an important toxicant of the pulmonary system in epigenetic insights. MicroRNA (miRNA) is an important indicator of biomedical risk assessment and target identification. Hexanal is highly detectable in the exhaled breath of patients with chronic obstructive pulmonary disease (COPD) and chronic inflammatory lung disease. In this study, we aimed to identify hexanal‐characterized miRNA‐mRNA correlations involved in lung toxicity. Microarray analysis identified 56 miRNAs that commonly changed their expression more than 1.3‐fold in three doses (600, 1000, and 1500 ppm) within hexanal‐exposed Fischer 344 rats by inhalation, and 226 genes were predicted to be target genes of miRNAs through TargetScan analysis. By integrating analyses of miRNA and mRNA expression profiles, we identified one anti‐correlated target gene (Chga; chromogranin A; parathyroid secretory protein 1). Comparative toxicogenomics database (CTD) analysis of this gene showed that Chga is involved with several disease categories such as cancer, respiratory tract disease, nervous system disease, and cardiovascular disease. Further research is necessary to elucidate the mechanisms of hexanal‐responsive toxicologic pathways at the molecular level. This study concludes that our integrated approach to miRNA and mRNA enables us to identify molecular events in disease development induced by hexanal in an in vivo rat model. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1909–1921, 2016.