Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Association between PCBs and lower embryonic weight in black-crowned night herons in San Francisco Bay

Reproductive problems, including congenital malformations, reduced hatching success, and decreased survival of hatchlings, have been observed in colonial-nesting water birds at the San Francisco Bay National Wildlife Refuge (SFBNWR). Twenty-four black-crowned night heron (Nycticorax nycticorax) eggs were collected from SFBNWR in 1983. Twelve of these were collected from separate nests when late-stage embryos were pipping, and an additional egg was randomly collected from each nest for organochlorine analysis. Overt anomalies and skeletal defects were not apparent. Embryonic weights (with partially absorbed yolk sacs removed) were 15% lower (p less than 0.05) in SFBNWR embryos compared to control embryos from the Patuxent Wildlife Research Center (PWRC). Crown-rump length and femur length were shorter for SFBNWR embryos. The geometric mean polychlorinated biphenyl (PCB) concentration in SFBNWR eggs was 4.1 ppm wet weight, with a range of 0.8-52.0 ppm. A negative correlation (r = -0.61; p less than 0.05) existed between embryonic weight and log-transformed PCB residues in whole eggs collected from the same nest at SFBNWR, suggesting a possible impact of PCBs on embryonic growth. A correlation with embryonic weight did not occur for DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene] residues. Liver microsomal aryl hydrocarbon hydroxylase activity was neither significantly elevated nor correlated with PCB, DDE, or PCB plus DDE log-transformed residues. It is unknown whether the apparent association between PCBs and lower weight is persistent through hatching.     

Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.     

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.