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Evaluation of the Dermal Irritancy of Chemicals
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
The indiscriminate use of definitive LD50 tests, i.e., determination of the dose of a particular compound necessary to kill 50% of exposed animals within a certain time under specified conditions, has been sharply criticized for needless waste of animal lives to obtain data with unwarranted precision and of limited value. Probably the second most commonly criticized procedure is the rabbit eye and skin irritation testing, the Draize test.15,20–25 An obvious answer to decreasing the number of animals used for dermal irritancy testing is to develop in vitro techniques. In vitro techniques have been, and will continue to be, developed, and are discussed in Chapter 9. With in vitro testing, however, one must still correlate the response measured with the effect seen in vivo, and the correlation determined for each chemical, or family of chemicals, may well not be the same for all compounds of interest. The same problem exists, obviously, for extrapolating results in laboratory animals to man. There is definitely a need for improved procedures to quantitatively and objectively assess the irritation potential of chemicals, and various ways in which such testing may be developed will be presented.
Contrast enhancement agents and radiopharmaceuticals
Published in A Stewart Whitley, Jan Dodgeon, Angela Meadows, Jane Cullingworth, Ken Holmes, Marcus Jackson, Graham Hoadley, Randeep Kumar Kulshrestha, Clark’s Procedures in Diagnostic Imaging: A System-Based Approach, 2020
A Stewart Whitley, Jan Dodgeon, Angela Meadows, Jane Cullingworth, Ken Holmes, Marcus Jackson, Graham Hoadley, Randeep Kumar Kulshrestha
The LD50 value is a number assigned to a pharmaceutical compound during development stages in clinical trials and relates to the median lethal dose for the substance to kill 50% of the test population. The free gadolinium ion has an LD50 of approximately 100–200 mg/kg, yet the LD50 is increased by a factor of 100 when the gadolinium is chelated. It is important to evaluate every patient and product for potential adverse side-effects before administering the contrast agent.
Herbs with Antidepressant Effects
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
The acute toxicity of coffee oil, arguably the most concentrated form of coffee phytochemicals, is low in toxicity with an oral LD50 in mice of 5 g/kg.26 The LD50 of orally administered caffeine in male albino rats is reported to be 367 mg/kg.27 This would extrapolate to about 25 g for a 75 kg human adult. Note that a strong cup of coffee contains about 125mg of caffeine.
Survival after intentional ingestion of highly concentrated, bulk nicotine solution
Published in Clinical Toxicology, 2021
Victoria Smith, Fauzia Ullah, Geoffrey Wall
A detailed review of symptoms and pathophysiology is provided elsewhere [2]. Signs and symptoms of nicotine toxicity are dose-dependent and biphasic, with an initial sympathetic presentation of salivation, tachycardia, and muscle contractions, followed by parasympathetic manifestations such as bradycardia from sympathetic receptor desensitization [2,3]. Nicotinic effects on the CNS, at neuromuscular junctions, and in the cardiovascular system can lead to seizures, respiratory failure, and cardiac arrest. Gastrointestinal symptoms are also observed in most oral ingestions. The usual reported median oral lethal dose (LD50) of nicotine in adults is 0.5–1 mg/kg, although recent literature has suggested a higher oral LD50 of 6.5–13 mg/kg [4,5]. The ingestion reported here of nicotine 75 mg/kg is greater than the dose reported in most surviving patients in the literature [2]. The patient’s positive outcome may be attributed partially to rapid escalation of care, which allowed him to avoid complications. This case illustrates the importance of prompt recognition and treatment of nicotine ingestion and the danger of highly concentrated bulk nicotine solutions.
Pre-clinical and cellular toxicity evaluation of 7-methylxanthine: an investigational drug for the treatment of myopia
Published in Drug and Chemical Toxicology, 2021
Harjeet Singh, Nikhil Shri Sahajpal, Harmanpreet Singh, Vanita Vanita, Partha Roy, Surinder Paul, Shashank Kumar Singh, Inderjit Kaur, Subheet Kumar Jain
In acute toxicity, the LD50 of 7-MX was found to be >2000 mg/kg in both rodent species. In comparison, LD50 of caffeine is reported to be 200–400 mg/kg in rat and 185 mg/kg in mouse (Caffeine CAS: 58-08-2), for theobromine LD50 is 950 mg/kg in rat and 1356 mg/kg in mouse. (Theobromine IAEC monograph). No mortality was observed in 7-MX treatment groups whereas, 66.6% (mice) and 33.3% (rat) mortality was observed on treatment with both caffeine and theobromine at their respective LD50 doses. Further, no behavioral changes were observed with 7-MX treatment. The probable poor brain permeability of 7-MX as per its structure activity relationship may be responsible for the absence of any behavioral toxic signs such as tremors, convulsions or coma. Thus, this grossly demonstrates no acute toxicity at both these doses.
Study of acute oral toxicity of the thiazole derivative N-(1-methyl-2-methyl-pyridine)-N-(p-bromophenylthiazol-2-yl)-hydrazine in a Syrian hamster
Published in Toxicology Mechanisms and Methods, 2021
Vinícius Vasconcelos Gomes de Oliveira, Mary Angela Aranda de Souza, Rafaela Ramos Mororó Cavalcanti, Marcos Veríssimo de Oliveira Cardoso, Ana Cristina Lima Leite, Regina Célia Bressan Queiroz de Figueiredo, Sebastião Rogério de Freitas Silva, Leucio Câmara Alves, Valdemiro Amaro da Silva Junior
Tests to assess acute toxicity are used to classify and label substances according to their toxicity or lethality (Valadares 2006). It is essential that these tests are conducted following internationally accepted protocols, such as those published by the OECD. In this study, the OECD 423 Guide (OECD 2001) was adopted. This method not only has good reproductivity, but also uses only few animals and is capable of classifying substances according to internationally accepted systems (Globally Harmonized System – GHS). The OECD 423 Guide (OECD 2001), together with the guides 420 and 425, replace the guide 401, introduced more than 50 years ago and which is no longer used by the OECD since 2001 (Valadares 2006). The latter, highly criticized by animal protection societies, statistically determines LD50 (the dose that kills 50% of the test population) from studies of groups of animals (typically 20 animals of both genders per group) exposed to increasing doses of the test substance.