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Animal Biotechnology
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2020
There are several different types of acute toxicity tests. The lethal dose 50 (LD50) test is used to evaluate the toxicity of a substance by determining the dose required to kill 50% of the test animal population. This test was removed from the Organization for Economic Co-operation and Development (OECD) international guidelines in 2002 and replaced by methods such as the fixed-dose procedure, which uses fewer animals and causes less suffering. The Humane Society of the United States writes that the procedure can cause redness, ulceration, hemorrhaging, cloudiness, or even blindness in animals. The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests are performed, lasting less than a month (acute), 1–3 months (subchronic), and more than 3 months (chronic) to test general toxicity (damage to organs), eye and skin irritancy, mutagenicity, carcinogenicity, teratogenicity, and reproductive problems. The cost of the full complement of tests is several million dollars per substance and it may take 3 or 4 years to complete.
Animal biotechnology
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2018
There are several different types of acute toxicity tests. The lethal dose 50 (LD50) test is used to evaluate the toxicity of a substance by determining the dose required to kill 50% of the test animal population. This test was removed from Organisation for Economic Co-operation and Development (OECD) international guidelines in 2002 and replaced by methods such as the fixed-dose procedure, which uses fewer animals and causes less suffering. The Humane Society of the United States writes that the procedure can cause redness, ulceration, hemorrhaging, cloudiness, or even blindness in animals. The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests are performed, lasting less than a month (acute), 1–3 months (subchronic), and more than 3 months (chronic) to test general toxicity (damage to organs), eye and skin irritancy, mutagenicity, carcinogenicity, teratogenicity, and reproductive problems. The cost of the full complement of tests is several million dollars per substance and it may take 3 or 4 years to complete.
Agricultural Sources of Micropollutants: from the Catchment to the Lake
Published in Nathalie Chèvre, Andrew Barry, Florence Bonvin, Neil Graham, Jean-Luc Loizeau, Hans-Rudolf Pfeifer, Luca Rossi, Torsten Vennemann, Micropollutants in Large Lakes, 2018
Silwan Daouk, Pierre-Jean Copin, Nathalie Chèvre, Hans-Rudolf Pfeifer
The herbicide, glyphosate [N-(phosphonomethyl)glycine], is the active ingredient of many herbicidal products, and represents the most used herbicide in the world. Globally, glyphosate sale volumes are estimated to be 600 kilotons annually (Dill et al., 2010). It is a broad-spectrum systemic herbicide which controls more than a hundred of annual and perennial weed species. It has the ability to translocate to meristematic plant tissues through phloem transport. It acts by inhibiting the enzyme, 5-enolpyruvyl- shikimate-3-phosphate synthase (EPSPS), involved in the synthesis of aromatic amino acids (Phenylalanine, Tyrosine, Tryptophan), which are essential for plant growth (Dill et al., 2010). As this metabolic pathway is present in plants, fungi and bacteria, but not in animals, glyphosate would theoretically exhibit low toxicity towards animals. Indeed, its median lethal dose ranges from 800 mg/kg to 1340 mg/kg in mammals, and from 1170 mg/kg to > 2000 mg/kg in amphibians (McComb et al., 2008). Several studies have shown, however, that glyphosate formulations (i.e., the commercial form of glyphosate) are more toxic and ecotoxic than the active ingredient itself (Tsui and Chu, 2003; Mann et al., 2009; Mesnage et al., 2014).
Random forest algorithm-based accurate prediction of rat acute oral toxicity
Published in Molecular Physics, 2022
Linrong Xiao, Jiyong Deng, Liping Yang, Xianwei Huang, Xinliang Yu
Determining acute toxicity of chemicals in mammals (e.g. rats or mice) is labor-intensive, high monetary and time cost. Furthermore, it is impossible to determine the toxicity of all chemicals [4,5]. Quantitative structure–activity relationship (QSAR)/quantitative structure–toxicity relationship models can be used for predicting the acute oral toxicity endpoint for compounds [6–10], even without necessarily carrying out their chemical synthesis. This methodology has been proposed in risk assessment by some regulations and guidelines like the European Union Registration, Evaluation and Authorization of Chemicals (EU REACH) Legislation, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 guideline, the United States Food & Drug Administration (US FDA) and the United States Environmental Protection Agency (US EPA) [11–14]. Mice and rats are by far the most common species used for experimental purposes [15–19]. The median lethal dose LD50 denotes the dose of a chemical resulting in 50% of mortality for a test group in a short amount of time (generally less than 24 h) [6,20]. Rat acute oral LD50 can serve useful functions and have practical implications. It has become a standard piece of information in categorising compounds in terms of the potential hazard affecting human health after acute exposure.
Synthesis of PEGylated cationic curdlan derivatives with enhanced biocompatibility
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Muqier Muqier, Hai Xiao, Xiang Yu, Yifeng Li, Mingming Bao, Qingming Bao, Shuqin Han, Huricha Baigude
In order to further confirm that PEGylation can reduce the toxicity of 6AC-100 and improve the biocompatibility, we first took the whole blood of C57/BL mice 24 h after the administration of 6AC-2S PEG40 by tail intravenous injection and measured the levels of ALT/AST in serum using 6AC-100 as a control (Figure 5(A)). It can be concluded that at the dose of 100 µg/mouse, the levels of ALT or AST of both 6AC-100 and 6AC-2S PEG40 treated group showed no significant difference compared with the NT group, but at the dose of 200 µg/mouse, the levels of ALT or AST of 6AC-100 were elevated, while 6AC-2S PEG40 showed no significant variation, indicating that 6AC-2S PEG40 has low toxicity in vivo. Next, we carried out an acute toxicity experiment to calculate LD50 values of the PEGylated curdlan derivatives. Again, 6AC-100 used as a control. LD50 is a term used in toxicology to measure the lethal dose of a substance. The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. This value is then used as an indicator of a substance’s relative toxicity. Thus, a substance with a high LD50 would have a low toxicity, while a substance with a low LD50 would have a high toxicity. The calculated results showed that 6.82 mg/kg doses of 6AC-100 killed half the mice, while 8.97 mg/kg doses of 6AC-2S PEG40 killed half the mice (Table 4, Figure 5(B)), indicating that 6AC-2S PEG40 was much less toxic compared to 6AC-100.
Good management practices of venomous snakes in captivity to produce biological venom-based medicines: achieving replicability and contributing to pharmaceutical industry
Published in Journal of Toxicology and Environmental Health, Part B, 2021
Lucilene Santos, Cristiano Oliveira, Barbara Marques Vasconcelos, Daniela Vilela, Leonardo Melo, Lívia Ambrósio, Amanda da Silva, Leticia Murback, Jacqueline Kurissio, Joeliton Cavalcante, Claudia Vilalva Cassaro, Luciana Barros, Benedito Barraviera, Rui Seabra Ferreira
Other reasons why these analytical techniques are relevant are to include whether the presence of disease affects the composition of venoms, and the types of captivity and food. These variables may or may not change the standard structural and toxicological profile of venoms (McCleary et al., 2016). One of these studies aimed to evaluate the chromatographic differences and lethal activity (LD50 – median lethal dose determination) of the snakes’ venoms of the Bothrops insularis species kept for 3 years in captivity at CEVAP compared to B. insularis living in the wild. After obtaining the chromatographic profiles, it was possible to observe quantitative variations in some fractions (Figure 10). For evaluation and comparison of lethal activity, the median lethal dose (LD50) in Mus musculus mice was used, where lethal activity data obtained was 76.5 mg/kg from venom of free-living snakes versus 68.6 mg/kg from captives. Thus, the observed results showed a difference of approximately 10% in the lethal activity of venoms from snakes kept in captivity compared to free-living snakes. However, to obtain a definitive conclusion from these differences, more studies of characterization, sequencing, and mass spectrometry are required. Data demonstrated the importance of the existence of ex-situ findings in relation to the study of lethal activity of venom and maintenance of all its protein characteristics.