Toxicity. Although cationic lipids are not immunogenic like viral vectors, they are not without any toxicity. They can be cytotoxic and the extent to which this is manifested differs between different reagents and cell types. The prospect of toxicity is determined by the nature of the cationic carrier as well as the cationic lipid/nucleic acid complex (Lv, H.T. et al., 2006). In terms of cationic lipid/nucleic acid complexes, the toxicity may, in part, be caused by the large size of the complexes, and the high positive zeta potential required for their uptake (Xx, S. et al., 1998, Lv, X.X. xx al., 2006). Therefore the toxicity is also associated with the charge ratio between the cationic lipid species and the nucleic acids, as well as the dose of lipoplexes administered. Higher +/-charge ratios are generally more toxic due to the high positive zeta potential as well as the presence of free (i.e., empty) liposomes (Xx, X. et al., 1999). Free liposomes are present at high charge ratios when lipid is in excess to nucleic acid but their role in transfection efficiency remains unclear. However, Xx et al (1999) showed that their removal did not increase transfection efficiency but did allowed prevention of a decrease in transfection-associated toxicity. Free liposomes may also compete with nucleic acid complexes for interaction with negatively charged membranes and uptake in cells.
Toxicity. Aim: To evaluate the overall toxicity of AE37 peptide vaccine in combination with pembrolizumab Endpoint: Frequency and severity of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Toxicity. Refer to the current AE-37 vaccine IB for safety and toxicity information.
Toxicity. Refer to the current pembrolizumab IB for toxicity information.
Toxicity. No additional information available *** Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. 1/22/2014 EN (English) 7/9 *** Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. Silica Sand Safety Data Sheet
Toxicity. During radiotherapy, any kind of side effect was reported in 26% of all irradiated patients (Table 3). Nineteen percent was grade 1 toxicity, representing only minor complaints. In 7% of the patients there was a grade 2 or 3 complication. Acute transient neurological complaints were recorded in 53 patients, of which 35 had grade 1, not requiring any intervention. In 2 patients the shielding was adjusted and the upper border was lowered in 3 patients. In 13 patients treatment was interrupted due to serious pain in the gluteal region or legs. Remarkably, of these 13 patients, 6 patients were treated in one radiation institute. No relation with number of portals, upper border, treatment position or shielding could be found. Due to the fact that the neurotoxicity score was introduced in 1997, data about neurotoxicity are missing in 178 patients. In four (<1%) patients other grade 3 toxicity was reported, leading to postponement of the operation in two patients with thrombo-embolic complications. One patient required a catheter due to urinary retention after the radiotherapy. The last patient had anal blood loss 2 months after radiotherapy and proctoscopy confirmed a proctitis. Table 3. Number of patients with radiotherapy toxicity. XXXX xxxxxxx 0 0 0 0 Skin 685 8 2 0 Gastrointestinal 605 75 14 1 Genitourinary 676 16 2 1 Neurological 464 35 5 13 Other 655 31 7 2 Table 4. Surgery characteristics. RT+TME TME n=695 n=719 n % n % P Operation characteristics time (median, range) 180 65-390 180 70-380 ns blood loss (median, range) 1100 50-20000 1000 20-15000 <0.001 LAR 1025 800 <0.001 APR 1200 1300 ns hospital stay (median, range) 15.0 3-179 14.0 0-169 ns Operation type when LAR planned LAR 408 85 435 89 ns APR 45 9 35 7 Xxxxxxxx 30 6 21 4 Stoma in LAR patients no stoma 176 36 216 43 0.05 stoma 263 64 249 57 Anastomosis in LAR patients side-end 261 60 278 60 ns end-end 54 12 50 11 pouch 122 28 132 29 missing 2 5 60 53 40 47 Operation time in minutes, blood loss in ml and hospital stay in days. ns=not significant To evaluate whether preoperative radiotherapy influences operation procedures, surgery characteristics are compared in Table 4. There was no significant difference in median operation time or median hospital stay between both treatment arms. Total blood loss was slightly increased (100 ml) in the irradiated (RT+) group (P<0.001). Subset analysis revealed that the difference in median blood loss was mainly present in the LAR patients: 1025 ml in the RT+ group ...
Toxicity. There is evidence based on the RAC opinion2 on UV-328 that indicates that the substance meets the criteria for classification as STOT RE 2 as defined in the CLP Regulation (EC) 1272/2008. As a consequence, the toxicity criterion of REACH Xxxxx XXXX is fulfilled.
Toxicity the liver, spleen, kidney, and heart will be examined by histology for necrosis or immune cell infiltrates. Above plan is to assess the effect of dexamethasone treatment on disease progression beginning from the onset phase. If needed, a similar plan will be followed for another group of mice in which efficacy of drug delivery to suppress a relapse flare will be tested. For TGFβ2, a similar plan will be followed as described above for dexamethasone.
Toxicity. Materials used in the CK shall not cause skin irritations or other injuries, and shall not produce vapor hazards, including the emission of toxic or noxious odors, to personnel in the CK under all environmental conditions.
Toxicity. A large data set on standard and non-standard long-term effect studies is available for TBT compounds. The lowest reliable chronic NOEC for TBT was identified to be 0.06 µg Sn l-1, corresponding to ca. 0.15 µg TBT l-1, for Daphnia magna. In addition to the very high toxicity in relation to conventional toxicity end- points, TBT compounds elicit effects in the endocrine systems of aquatic organisms. The mollusc species Nucella lapillus (dog whelk) is the most sensitive species to tributyltin compounds. A LOEC of 0.002 µg l-1 was obtained in a 360-d study looking at imposex (NOEC < 0.002 µg l-1). TBT compounds are considered to fulfil the T criterion for ecotoxicity. Moreover tributyltin compounds are classified as toxic; danger of serious damage to health by prolonged exposure through inhalation and if swallowed (T; 48/23/25) and TBTO therefore fulfils also the T criterion for human health. In the impact assessment of potential restrictions on the marketing and use of certain organotin compounds it is concluded that, in relation to the marine environment, TBT is likely to be classified as both PBT and vPvB substance.
