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In Vitro Methods: Alternatives to Animal Testing
Published in Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters, Cosmetic Formulation, 2019
Dayane Pifer Luco, Vânia Rodrigues Leite-Silva, Heather A.E. Benson, Patricia Santos Lopes
The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM 2006a,b,c) proposed a cytotoxicity test in February 2008. An IC50 value (half maximal inhibitory concentration, that is, the concentration of a substance needed to inhibit a given biological process [or component of a process, such as an enzyme, cell, cell receptor or microorganism] by half) from an in vitro basal cytotoxicity test is used with the linear regression equation (Registry of Cytotoxicity [RC] regression) to predict the oral LD50 value (half‑lethal dose, or the individual dose required to kill 50% of a test population). The predicted LD50 is used as the starting dose for the acute toxic class (ATC) method or the up-and-down procedure (UDP) test method (Spielmann et al., 1999), and as a first test for all the other cosmetic ingredient in vitro tests. Thus the oral LD50 for acute oral systemic toxicity is determined.
Acute Toxicity Testing by the Dermal Route
Published in Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach, Health Risk Assessment, 2017
Roy C. Myers, Lin val R. DePass
There are several other methods that may be used to calculate LD50s, many of which are designed to use minimal numbers of animals. These have received varying degrees of acceptance by toxicologists and regulators. One method is the Up-And-Down Procedure.93,94 In this method, animals are dosed one at a time. If the animal survives, a second animal receives a higher dose. If the first animal dies, a second animal receives a lower dose. This process continues until several lethal and nonlethal levels, separated by a relatively small factor, are obtained. Then, a series of calculations is used to determine an LD50 value. In a method published by Lorke,95 three animals are administered each of three widely spaced doses (10, 100, and 1000 mg/kg). The results of this phase of the test are used to establish a second set of doses (usually three or four) which are more closely spaced. One animal may be sufficient for each of the second set of dose levels. The LD50 may then be estimated by standard calculations. Schütz and Fuchs96 have proposed a method using a small number of animals (two or three per sex per group), but with extended observation times and multiple probe doses.
Biochemical and histopathological analysis after sub-chronic administration of oxyresveratrol in Wistar rats
Published in Drug and Chemical Toxicology, 2023
Nisat Alam, Hasina Najnin, Maidul Islam, Sonam Shakya, Ishaat M. Khan, Rana Zaidi
Ten female Wistar albino rats weighing 90–100 g (age 8–9 weeks) were selected for the acute oral toxicity study. The experiment was performed according to the OECD (Organization for Economic Cooperation and Development) guideline 425, ‘Up and Down Procedure’ (OECD, 2008). Rats were fasted overnight and OXY was administered orally in a single dose (2000 mg/kg B.W.) to the treatment group (n = 5). Changes in body weight were recorded before OXY administration and on the second, sixth, tenth, and fourteenth days after OXY administration, respectively. Mortality and other physical and behavioral alterations like diarrhea, tremors, lethargy, salivation, and convulsions were individually observed in all animals for 14 days, specially focusing for the first 30 minutes after OXY administration. Consequent effects in eyes, fur, skin, respiratory, mucous membranes, nervous and circulatory systems were also monitored. After 14 days, rats were fasted overnight and euthanized by CO2 gas asphyxiation followed by intracardiac exsanguination. Gross pathological examination of different organs and tissues was performed for each animal.
The Finnish simplified matrix sentence test for the assessment of speech intelligibility in the elderly
Published in International Journal of Audiology, 2020
Tytti Willberg, Karissa Kärtevä, Melanie Zokoll, Michael Buschermöhle, Ville Sivonen, Antti Aarnisalo, Heikki Löppönen, Birger Kollmeier, Aarno Dietz
The aim of the evaluation measurements was to confirm the equal intelligibility of the test lists, and to provide a reference value for NH YA. The reference values were determined using word scoring, and the A1 adaptive procedure used by the OLSA-based matrix tests (Brand and Kollmeier 2002). The procedure was designed to first quickly reach the range of the speech reception threshold (SRT) estimate, and then to stabilise the presentation level close to the actual SRT to increase the accuracy of the SRT estimation. It uses a 1-up-1-down procedure where the step size varies based on the number of words correctly recognised during the previous sentence. At the same time, the rate of convergence decreases as the number of reversals in the adaptive track increases. The SRT for each test list is estimated by using the maximum likelihood method to fit the test-specific intelligibility function to the data obtained during the presentation of a test list (Wagener, Brand, and Kollmeier 1999a,b; Kollmeier et al. 2015).
DMTS is an effective treatment in both inhalation and injection models for cyanide poisoning using unanesthetized mice
Published in Clinical Toxicology, 2018
Susan M. DeLeon, Jason D. Downey, Diane M. Hildenberger, Melissa O. Rhoomes, Lamont Booker, Gary A. Rockwood, Kelly A. Basi
A total of 12 age-matched unanesthetized male mice were challenged with DMTS via IM injection in the left caudal thigh and monitored for toxic signs. The median lethal dose, LD50, of DMTS toxicity in mice was determined via the up-and-down procedure (UDP) sequential testing method [34]. Starting with a dose of 400 mg/kg DMTS, the dose of each successive animal was adjusted either up or down, depending on the outcome of the previous animal. If the previous animal survived, the successive dose in the next subject was increased at 0.1 log unit interval (Table S1). If the animal died, the successive dose was decreased at 0.1 log unit interval. The stopping criterion consisted of 5 reversals in responses. A total of nine animals were used to achieve the stopping criterion for the DMTS LD50 dose determination. To further characterize the observed clinical signs at specific doses following the LD50 dose determination, three additional mice were challenged with DMTS at various doses and examined for the presence or absence of clinical signs within a 24-hour period following exposure.