Toxicological pathology of cockleburs (Xanthium spp.) for broiler chickens.

Spiking mortality syndrome (SMS) in chickens resembles cocklebur toxicity in cattle, sheep, pigs, and rats. In order to determine if cockleburs are toxic to broiler chicks, crushed burs were fed (25% wt:wt) to broilers for 21 days. Ingestion of cockleburs resulted in significant failure to properly gain body weight. Otherwise, chicks did not develop clinical signs of illness or gross or microscopic lesions. Although there were some significant differences in serum chemistry values among chick groups, there were no consistent patterns. Severe hypoglycemia is said to be a characteristic finding in chicks that die with SMS. Because glucose levels were not low in chicks that were fed cockleburs, we feel certain that cockleburs do not cause SMS.     

Streptozotocin-induced diabetes decreases placenta growth factor (PlGF) levels in rat placenta

The placenta produces several growth factors, including placenta growth factor (PlGF), which are essential for placenta growth and fetal growth. Diabetic pregnancy induces the abnormal placental growth and fetal development. This study investigated whether diabetes in pregnant rats induces changes in PlGF expression in the placenta. Diabetes was induced by a single intravenous injection of streptozotocin (35 mg/kg body weight) on day 0 of pregnancy, blood and tissue samples were collected on day 20 of pregnancy. In the diabetic group, maternal body weight and fetal weight significantly decreased compared to controls. RT-PCR and Western blot analyses showed that expression of PlGF was significantly decreased in placenta by streptozotocin treatment. Immunohistochemical study showed that the positive signal of PlGF in trophoblast cells was decreased in the diabetic group compared to controls. These findings demonstrate the decline of PlGF in the placenta in diabetic pregnancy.     

Effect of 6-mercaptopurine on rat placenta

In order to investigate the toxic effects of 6-mercaptopurine (6-MP) on placental development, we examined sequential morphology in the placentas from rats exposed to 6-MP. 6-MP was intraperitoneally administered at 60 mg/kg during gestation days (GDs) 11 to 12, and the placentas were sampled on GD 13, 15 or 21. In the 6-MP-treated group, maternal body weight suppression, increased death embryo/fetus ratio and some malformations were observed. The placenta weights were decreased on GDs 15 and 21. Macroscopically, placentas on GD 21 were small, brittle and thin with a white peripheral rim. Histopathologically, in the labyrinth zone, 6-MP treatment mainly evoked decreased mitosis on GDs 13 and 15, increased apoptotic cell on GDs 13, 15 and 21 and thinning on GDs 15 and 21. In the basal zone, 6-MP evoked decreased mitosis on GDs 13, and PAS-positive material in the spongiotrophoblasts was still detected on GD 15. Thickening of the basal zone was observed with cytolysis of glycogen cells, apoptosis and an increased number of composed cells on GD 21. In conclusion, 6-MP administration in pregnant rats induced growth arrest of the labyrinth zone and developmental delay in the basal zone, leading to small placentas. The fetotoxicity of 6-MP may be responsible for its direct anti-proliferative effects and resulting placental dysfunction.     

Toxicological properties of metaflumizone

Metaflumizone is a new insecticide developed for crop protection and urban pest control by BASF. Its mammalian toxicological profile was assessed by conducting multiple toxicity studies in the rat, mouse, and dog, covering all relevant endpoints. Metaflumizone is characterized by very low acute toxicity, is not irritating to the eye or the skin and does not possess a potential to induce skin sensitization. The substance also shows relatively low toxicity following subchronic oral or dermal exposure to mammals. In addition, metaflumizone demonstrates low toxicological potential following chronic oral exposure to rats, mice, and dogs. Overall, the lowest no observed adverse effect level (NOAEL) is 12mg/(kgday) from the 1-year chronic dog study. In a battery of in vitro and in vivo mutagenicity assays, the weight-of-the-evidence indicates a lack of potential genotoxicity for metaflumizone. Furthermore, the compound demonstrated a lack of potential oncogenicity in long-term toxicity studies in rats and mice. Results from the rat multi-generation reproductive toxicity study as well as the rat and rabbit developmental toxicity studies indicate that metaflumizone is not selectively toxic to the offspring or fetus, as compared to the parents. Also, metaflumizone is not teratogenic in the rat or rabbit. Lastly, no neurotoxicity could be detected in acute and subchronic neurotoxicity studies in rats.     

Toxicological Studies of Phenoxyacetic Herbicides in Animals

The main purpose of the present work was to study the long-term effects of 2,4-dichlorophenoxyacetic acid (2,4-D) in swine, rats and chickens.In preliminary short-term experiments with calves and pigs, definite although reversible toxic effects were seen after single doses of 200 and 100 mg/kg, respectively. Rats and chickens seemed to tolerate 100 and 300 mg/kg, respectively, without ill-effects. On repeated administration daily doses of 50 mg/kg could be toxic to pigs, whereas chickens tolerated 300 mg/kg/day for several weeks without visible effects. Symptoms of acute poisoning in calves were dysphagia, anorexia, tympanites and muscular weakness. Anorexia was apparent also in acutely or subacutely poisoned pigs together with locomotory disturbances, transient diarrhoea and, in severe cases, vomiting, muscular weakness and general depression. In all animals showing symptoms of poisoning a reduced disappearance rate of 2,4-D from plasma was apparent. On autopsy the pigs showed signs of gastro-intestinal irritation and pneumonia and renal degeneration. In the rats and chickens no gross pathological changes were seen.In the long-term studies 5 young pigs were fed 2,4-D (500 p.p.m.) for up to 12 months. Main clinical signs were growth depression, locomotory disturbances, anaemia and albuminuria. Morphological changes included moderate hepatic and renal degeneration. In another experiment 2,4-D was fed to a pregnant sow throughout the gestation period and for 6 further weeks. The sow exhibited no characteristic signs, and on autopsy no changes attributable to 2,4-D were noted. The newborn piglets, however, were underdeveloped and apathetic. Ten out of 15 died within 24 hours. On continued feeding of 2,4-D to the survivors until 7–8 months of age the main effects were a marked growth depression, persistent anaemia and moderate degenerative changes of liver and kidneys.Pregnant rats were given 2,4-D (1000 p.p.m.) in the drinking water during the gestation and further for up to 10 months. The administration of 2,4-D was continued to the second generation rats for up to 2 years. Except for a retarded growth and an increased mortality in the second generation no unequivocal clinical or morphological changes were seen.In chickens continued administration of 2,4-D (500 p.p.m. in the feed or 1000 p.p.m. in the drinking water) caused a reduced eggproduction and pronounced kidney enlargement due to epithelial proliferations, this latter lesion appearing only when very young chicks were used as experimental animals.The experimental results indicate the chronic toxicity of 2,4-D for the species examined to be moderate. Apart from the nephrotoxicity demonstrated in chicks the long-term effects were non-specific. Of particular interest, however, are the high mortality in the newborn piglets and the reduced egg production in the chickens as indications of a possible interference with reproduction.     

Toxicological Emergencies in Fish Products: Introduction

Veterinary Research Communications -     

Toxicological hazards in warble fly eradication programmes

This paper reviews the experience of the last decade involving the large-scale use of systemic organophosphorus insecticides for the control of the warble fly (Hypoderma spp.). The information is drawn from the so far unique national eradication programme in Eire and from other countries where these products have been widely used.An attempt is made to differentiate between direct toxic effects of the drug used, reactions due to parasite destruction, and disease processes circumstantially associated with the treatment.It is emphasized that, for an eradication programme to be successful, several criteria must be met. (1) The stock owners must clearly recognize the slight, but always present, toxicological hazard. Such toxicities are not always easy to anticipate or diagnose. (2) Adequate compensation must be available to satisfy genuine claims for death or financial loss. (3) An efficient and acceptable service must be available to investigate complaints quickly and effectively.     

NAS制剂毒理学研究

为了评价NAS制剂的毒性,以小白鼠、雏鸡进行了毒理学试验研究。急性毒性试验结果表明,小鼠口服NAS中草药制剂的LD50为（9．0573±0.0309）g／kg。亚慢性毒性试验结果表明,3个剂量组（1．8g／kg,0．45s／ks,0．15s／ks）雏鸡连续口服NAS中草药制剂14d,1次／d,未出现中毒症状,而显示出有增重作用,且增重率与药物剂量成正比,即高剂量组〉中剂量组〉低剂量组。     

Metabolic Fingerprinting in Toxicological Assessment Using FT-ICR MS

Detection of the toxicity of a candidate compound at an early stage of drug development is an emerging area of interest. It is difficult to determine all of the effects of metabolism of a compound using traditional approaches such as histopathology and serum biochemistry. The goal of a metabolomics approach is to determine all metabolites in a living system, with the potential to detect and identify biomarkers involved in toxicity onset. Here, we summarize the metabolic fingerprints for detection and identification of metabolic changes and biomarkers related to drug-induced toxicity using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS).