The document describes guidelines for toxicological screening methods from the Organisation for Economic Co-Operation and Development (OECD). It outlines various OECD guidelines for toxicity studies including acute oral toxicity, acute dermal toxicity, skin sensitization, acute eye irritation, inhalation toxicity, reproduction/developmental toxicity screening, carcinogenicity studies, prenatal developmental toxicity studies, and genetic toxicology studies. It then describes the methods, measurements, time course studies, and data reporting for conducting toxicological screening studies.
Experimental evaluation of anti inflammatory agentsAditi Panditrao
This document discusses methods for evaluating anti-inflammatory agents both in vitro and in vivo. It describes several in vitro assays including receptor binding assays for bradykinin and substance P, assays measuring polymorphonuclear leukocyte chemotaxis and aggregation, and assays examining the effects on arachidonic acid metabolism and cytokine production. In vivo models discussed include paw edema, ear edema, vascular permeability, and granuloma formation assays to evaluate different phases of inflammation. The document also covers methods for assessing potential side effects like ulcerogenicity.
Preclinical screening methods of Sedative and hypnotics by syedMubasheer syed
This document discusses preclinical screening methods for sedative and hypnotic drugs. It describes physiology of sleep and the basic pharmacology of sedative-hypnotics. In vivo screening methods are outlined, including open field tests to measure sedation and hole board tests or combined open field tests to measure sedation and curiosity. Tests to measure hypnotic effects include potentiation of hexobarbital sleeping time and experimental insomnia in rats. In vitro screening methods like EEG registration in conscious cats and automated rat sleep analysis are also summarized. The document provides an overview of preclinical tests used to characterize new sedative and hypnotic compounds.
Invivo screening methods for anti inflammatory agentsSravani Ganti
This document describes various in vivo screening methods used to test potential anti-inflammatory agents. It discusses acute, subacute, and chronic inflammation phases and associated screening methods. Methods described include carrageenan-induced paw edema in rats, croton-oil induced ear edema in mice, oxazolone induced ear edema in mice, UV erythema in guinea pigs, pleurisy test, granuloma pouch technique, and vascular permeability test. Each method involves inducing inflammation and measuring the ability of test compounds to reduce inflammatory responses like edema formation compared to control groups.
This document describes various in vivo and in vitro models used to study antihypertensive and vasodilator drugs. In vivo models include the Goldblatt hypertension model in rats, chronic renal hypertension in rats and dogs, and the tail cuff method in rats. In vitro models include ACE inhibition in guinea pig ileum and β1 sympatholytic activity in guinea pig atria. The document also provides details of the procedures for these models.
The document provides guidance on testing the acute dermal irritation and corrosion of chemicals using rabbits. It describes how to handle and restrain rabbits, introduces the principles and objectives of the test which involves applying chemicals to rabbit skin and observing effects. It details the test procedures including animal selection and housing, chemical application, observation periods and grading of skin reactions on a scale. The test aims to identify reversible irritation and irreversible corrosion effects of chemicals on rabbit skin to classify them.
Experimental evaluation of anti inflammatory agentsAditi Panditrao
This document discusses methods for evaluating anti-inflammatory agents both in vitro and in vivo. It describes several in vitro assays including receptor binding assays for bradykinin and substance P, assays measuring polymorphonuclear leukocyte chemotaxis and aggregation, and assays examining the effects on arachidonic acid metabolism and cytokine production. In vivo models discussed include paw edema, ear edema, vascular permeability, and granuloma formation assays to evaluate different phases of inflammation. The document also covers methods for assessing potential side effects like ulcerogenicity.
Preclinical screening methods of Sedative and hypnotics by syedMubasheer syed
This document discusses preclinical screening methods for sedative and hypnotic drugs. It describes physiology of sleep and the basic pharmacology of sedative-hypnotics. In vivo screening methods are outlined, including open field tests to measure sedation and hole board tests or combined open field tests to measure sedation and curiosity. Tests to measure hypnotic effects include potentiation of hexobarbital sleeping time and experimental insomnia in rats. In vitro screening methods like EEG registration in conscious cats and automated rat sleep analysis are also summarized. The document provides an overview of preclinical tests used to characterize new sedative and hypnotic compounds.
Invivo screening methods for anti inflammatory agentsSravani Ganti
This document describes various in vivo screening methods used to test potential anti-inflammatory agents. It discusses acute, subacute, and chronic inflammation phases and associated screening methods. Methods described include carrageenan-induced paw edema in rats, croton-oil induced ear edema in mice, oxazolone induced ear edema in mice, UV erythema in guinea pigs, pleurisy test, granuloma pouch technique, and vascular permeability test. Each method involves inducing inflammation and measuring the ability of test compounds to reduce inflammatory responses like edema formation compared to control groups.
This document describes various in vivo and in vitro models used to study antihypertensive and vasodilator drugs. In vivo models include the Goldblatt hypertension model in rats, chronic renal hypertension in rats and dogs, and the tail cuff method in rats. In vitro models include ACE inhibition in guinea pig ileum and β1 sympatholytic activity in guinea pig atria. The document also provides details of the procedures for these models.
The document provides guidance on testing the acute dermal irritation and corrosion of chemicals using rabbits. It describes how to handle and restrain rabbits, introduces the principles and objectives of the test which involves applying chemicals to rabbit skin and observing effects. It details the test procedures including animal selection and housing, chemical application, observation periods and grading of skin reactions on a scale. The test aims to identify reversible irritation and irreversible corrosion effects of chemicals on rabbit skin to classify them.
This document describes several models used to test anti-inflammatory activity, including acute and chronic inflammation models. Acute inflammation models include carrageenan-induced paw edema, croton oil ear edema, and ultraviolet erythema, which measure edema or redness caused by inflammatory agents. Chronic models include cotton pellet-induced granuloma, which measures granuloma formation over 7 days. These models are used to evaluate a test compound's ability to reduce inflammation induced by substances like carrageenan, croton oil, or UV light by measuring paw/ear swelling or granuloma weight. The anti-inflammatory effect is calculated as a percentage reduction compared to controls.
This document summarizes screening methods for evaluating potential anti-inflammatory drugs. It discusses the inflammatory response and various animal models used to test drug candidates, including carrageenan-induced paw edema, cotton pellet-induced granuloma, and UVB-induced erythema in guinea pigs. Several in vitro assays are also described, such as measuring COX inhibition and evaluating the ability of drugs to block mast cell degranulation and platelet-neutrophil adhesion. The goal of these screening methods is to effectively identify drug candidates that can target different phases and components of the inflammatory process.
toxicology study according to OECD guidelines, organisation for economic co-orporation and developement, jasdeep singh , maharaja ranjit singh punjab technical university bathinda
This document describes various methods for screening anti-emetic drugs, including animal models that induce nausea and vomiting through chemicals like cisplatin, methotrexate, apomorphine, copper sulfate, motion, and radiation. Parameters assessed in the animal models include behavioral changes, latency to first retching and vomiting, and number of vomiting episodes. The document also mentions in vitro models can be used to test new anti-emetic drugs' ability to antagonize 5-HT3 receptors, which are the most potent targets of existing anti-emetics.
screening methods for Antinflammatory drugs slide shareAnkitha868680
This document summarizes screening methods for anti-inflammatory drugs, including both in vivo and in vitro methods. Some key in vivo methods described are the carrageenan-induced paw edema test in rats, which detects orally active anti-inflammatory agents, and the croton oil-induced ear edema test in mice, used to detect anti-inflammatory activity of steroids. Important in vitro methods include assays measuring inhibition of human red blood cell hemolysis, bradykinin receptor binding, and arachidonic acid metabolism. The document provides details on procedures and evaluation of several standard screening tests used to evaluate potential new anti-inflammatory compounds.
Screening method of nootropics vikas malikVikasMalik68
1. The document describes various methods for screening nootropic substances, including in vivo, in vitro, and molecular-level experiments.
2. Some key in vivo methods discussed are passive avoidance testing in rats/mice, active avoidance conditioning experiments, and electrophysiological studies like long-term potentiation experiments in hippocampal brain slices.
3. In vitro screening methods outlined involve measuring inhibition of acetylcholinesterase activity from rat brain tissue and butyrylcholinesterase activity from human serum. Molecular-level experiments involve analyzing effects on acetylcholine receptors and neurotransmitter release.
This document describes various in vivo and in vitro screening methods used to evaluate potential analgesic compounds. Some key in vivo methods include the tail flick test, hot plate test, and acetic acid-induced writhing test, which assess analgesic effects using thermal, mechanical, and chemical pain stimuli, respectively. Important in vitro assays involve measuring the inhibition of nociceptin, binding to opioid receptors, and inhibition of enkephalinase enzyme. The screening methods aim to distinguish between narcotic and non-narcotic analgesics and help identify new compounds for treating different pain states.
This document provides information on screening methods for antidiabetic drugs. It discusses various in vivo and in vitro models used to screen drugs, including chemically-induced diabetes models using alloxan and streptozotocin in animals, genetically diabetic animal models like NOD mice and BB rats, and isolated tissue and cell-based in vitro models. A variety of animal models aim to mimic types 1 and 2 diabetes by destroying pancreatic beta cells or inducing insulin resistance. These preclinical models are used to evaluate new drugs' ability to lower blood glucose levels and treat diabetes symptoms before human trials.
The document discusses various methods for screening hepatoprotective drugs. It describes in vitro models using primary hepatocyte cultures, hepatic stellate cell cultures, and assays measuring proline hydroxylation inhibition. In vivo models inducing liver injury in rats are also outlined, including models using Long Evans Cinnamon rats, hepatic ischemia, allyl alcohol, carbon tetrachloride, and galactosamine. The goal of these screening methods is to evaluate potential drug candidates for protecting against liver toxicity and damage.
This document summarizes screening models used to evaluate potential aphrodisiac agents. It describes various in vivo and in vitro animal models, including tests of mating behavior, libido, potency, penile microcirculation, intracavernous pressure, and more. Guidelines for conducting the studies in animals are provided. Evaluation methods like determining hormone levels, nitric oxide release, organ weights and histology are also mentioned. The document aims to explain the process of evaluating aphrodisiac agents from experimental animal studies to clinical trials.
This document summarizes models used to study anti-emetic drugs. It describes various in vivo, in vitro, and human models. For in vivo models, it outlines drug-induced (cisplatin, apomorphine, copper sulfate), motion, and radiation models using species like dogs, cats, ferrets, and rats. It discusses parameters assessed like retching episodes. For in vitro models, it notes evaluating drugs' activity at 5-HT3 receptors. Finally, it mentions human models like using apomorphine or ipecac to induce vomiting and assessing drug effectiveness.
Pharmacological screening of analgesic activityBiswash Sapkota
1. The document describes several screening methods used to evaluate potential analgesic agents, including in vivo models using thermal, electrical, or chemical stimuli to induce pain states in animals, as well as in vitro receptor binding assays.
2. Common in vivo models discussed are the hot plate test, tail flick test, writhing test induced by acetic acid injection, and formalin test, which create persistent pain.
3. Details are provided on procedures for these tests, which involve administering a potential analgesic and measuring its ability to delay pain-induced responses like paw licking or jumping.
This document summarizes screening methods for evaluating the antipyretic (fever-reducing) effects of drugs in animal models. It describes using the Brewer's yeast suspension method to induce fever in rats and rabbits, and then testing potential antipyretic drugs. Key points:
1) Drugs are given to fevered animals and temperatures recorded at intervals to see if drugs lower elevated body temperatures compared to controls.
2) Studies summarized evaluated antipyretic effects of extracts from Bauhinia racemosa and Gracilaria corticata seaweed in rats. Both produced significant antipyretic activity.
3) The rabbit model uses bacterial lipopolysaccharides to induce fever and tests
This document summarizes screening models used to test centrally and peripherally acting muscle relaxants. It describes in vivo models using mice to test drugs' effects on inclined plane, chimney, grip strength, and rota rod tests. For peripherally-acting drugs, it outlines ex vivo phrenic nerve-diaphragm and sciatic nerve-gastrocnemius muscle preparations to assess muscle contraction responses. The rabbit head drop method evaluates centrally-acting drugs' abilities to relax neck muscles supporting the head.
This document discusses toxicity testing and provides details about various toxicity studies. It explains that toxicity testing involves observing adverse effects of chemicals in living organisms. It then describes different types of toxicity studies including acute, sub-acute, sub-chronic, chronic, and carcinogenicity studies. The document provides details about parameters evaluated in acute and chronic toxicity studies such as dosage, duration, symptoms observed, and endpoints. It also discusses alternative methods to traditional animal testing and guidelines for reporting toxicity study results.
Initial considerations for the study design include information on the test chemical's identity, properties, and results from previous toxicity tests. The guideline describes conducting a chronic toxicity study in rodents for 12 months, with the potential for interim kills and satellite groups. Key steps include dosing animals daily, observing them for signs of toxicity, and conducting clinical pathology, including hematology, clinical biochemistry, and urinalysis at various times. At the end, a full gross necropsy is performed and tissues are examined microscopically. Results are reported individually and summarized, including survival, body weights, food consumption, toxic responses, organ weights, and histopathological findings.
This document describes several models used to test anti-inflammatory activity, including acute and chronic inflammation models. Acute inflammation models include carrageenan-induced paw edema, croton oil ear edema, and ultraviolet erythema, which measure edema or redness caused by inflammatory agents. Chronic models include cotton pellet-induced granuloma, which measures granuloma formation over 7 days. These models are used to evaluate a test compound's ability to reduce inflammation induced by substances like carrageenan, croton oil, or UV light by measuring paw/ear swelling or granuloma weight. The anti-inflammatory effect is calculated as a percentage reduction compared to controls.
This document summarizes screening methods for evaluating potential anti-inflammatory drugs. It discusses the inflammatory response and various animal models used to test drug candidates, including carrageenan-induced paw edema, cotton pellet-induced granuloma, and UVB-induced erythema in guinea pigs. Several in vitro assays are also described, such as measuring COX inhibition and evaluating the ability of drugs to block mast cell degranulation and platelet-neutrophil adhesion. The goal of these screening methods is to effectively identify drug candidates that can target different phases and components of the inflammatory process.
toxicology study according to OECD guidelines, organisation for economic co-orporation and developement, jasdeep singh , maharaja ranjit singh punjab technical university bathinda
This document describes various methods for screening anti-emetic drugs, including animal models that induce nausea and vomiting through chemicals like cisplatin, methotrexate, apomorphine, copper sulfate, motion, and radiation. Parameters assessed in the animal models include behavioral changes, latency to first retching and vomiting, and number of vomiting episodes. The document also mentions in vitro models can be used to test new anti-emetic drugs' ability to antagonize 5-HT3 receptors, which are the most potent targets of existing anti-emetics.
screening methods for Antinflammatory drugs slide shareAnkitha868680
This document summarizes screening methods for anti-inflammatory drugs, including both in vivo and in vitro methods. Some key in vivo methods described are the carrageenan-induced paw edema test in rats, which detects orally active anti-inflammatory agents, and the croton oil-induced ear edema test in mice, used to detect anti-inflammatory activity of steroids. Important in vitro methods include assays measuring inhibition of human red blood cell hemolysis, bradykinin receptor binding, and arachidonic acid metabolism. The document provides details on procedures and evaluation of several standard screening tests used to evaluate potential new anti-inflammatory compounds.
Screening method of nootropics vikas malikVikasMalik68
1. The document describes various methods for screening nootropic substances, including in vivo, in vitro, and molecular-level experiments.
2. Some key in vivo methods discussed are passive avoidance testing in rats/mice, active avoidance conditioning experiments, and electrophysiological studies like long-term potentiation experiments in hippocampal brain slices.
3. In vitro screening methods outlined involve measuring inhibition of acetylcholinesterase activity from rat brain tissue and butyrylcholinesterase activity from human serum. Molecular-level experiments involve analyzing effects on acetylcholine receptors and neurotransmitter release.
This document describes various in vivo and in vitro screening methods used to evaluate potential analgesic compounds. Some key in vivo methods include the tail flick test, hot plate test, and acetic acid-induced writhing test, which assess analgesic effects using thermal, mechanical, and chemical pain stimuli, respectively. Important in vitro assays involve measuring the inhibition of nociceptin, binding to opioid receptors, and inhibition of enkephalinase enzyme. The screening methods aim to distinguish between narcotic and non-narcotic analgesics and help identify new compounds for treating different pain states.
This document provides information on screening methods for antidiabetic drugs. It discusses various in vivo and in vitro models used to screen drugs, including chemically-induced diabetes models using alloxan and streptozotocin in animals, genetically diabetic animal models like NOD mice and BB rats, and isolated tissue and cell-based in vitro models. A variety of animal models aim to mimic types 1 and 2 diabetes by destroying pancreatic beta cells or inducing insulin resistance. These preclinical models are used to evaluate new drugs' ability to lower blood glucose levels and treat diabetes symptoms before human trials.
The document discusses various methods for screening hepatoprotective drugs. It describes in vitro models using primary hepatocyte cultures, hepatic stellate cell cultures, and assays measuring proline hydroxylation inhibition. In vivo models inducing liver injury in rats are also outlined, including models using Long Evans Cinnamon rats, hepatic ischemia, allyl alcohol, carbon tetrachloride, and galactosamine. The goal of these screening methods is to evaluate potential drug candidates for protecting against liver toxicity and damage.
This document summarizes screening models used to evaluate potential aphrodisiac agents. It describes various in vivo and in vitro animal models, including tests of mating behavior, libido, potency, penile microcirculation, intracavernous pressure, and more. Guidelines for conducting the studies in animals are provided. Evaluation methods like determining hormone levels, nitric oxide release, organ weights and histology are also mentioned. The document aims to explain the process of evaluating aphrodisiac agents from experimental animal studies to clinical trials.
This document summarizes models used to study anti-emetic drugs. It describes various in vivo, in vitro, and human models. For in vivo models, it outlines drug-induced (cisplatin, apomorphine, copper sulfate), motion, and radiation models using species like dogs, cats, ferrets, and rats. It discusses parameters assessed like retching episodes. For in vitro models, it notes evaluating drugs' activity at 5-HT3 receptors. Finally, it mentions human models like using apomorphine or ipecac to induce vomiting and assessing drug effectiveness.
Pharmacological screening of analgesic activityBiswash Sapkota
1. The document describes several screening methods used to evaluate potential analgesic agents, including in vivo models using thermal, electrical, or chemical stimuli to induce pain states in animals, as well as in vitro receptor binding assays.
2. Common in vivo models discussed are the hot plate test, tail flick test, writhing test induced by acetic acid injection, and formalin test, which create persistent pain.
3. Details are provided on procedures for these tests, which involve administering a potential analgesic and measuring its ability to delay pain-induced responses like paw licking or jumping.
This document summarizes screening methods for evaluating the antipyretic (fever-reducing) effects of drugs in animal models. It describes using the Brewer's yeast suspension method to induce fever in rats and rabbits, and then testing potential antipyretic drugs. Key points:
1) Drugs are given to fevered animals and temperatures recorded at intervals to see if drugs lower elevated body temperatures compared to controls.
2) Studies summarized evaluated antipyretic effects of extracts from Bauhinia racemosa and Gracilaria corticata seaweed in rats. Both produced significant antipyretic activity.
3) The rabbit model uses bacterial lipopolysaccharides to induce fever and tests
This document summarizes screening models used to test centrally and peripherally acting muscle relaxants. It describes in vivo models using mice to test drugs' effects on inclined plane, chimney, grip strength, and rota rod tests. For peripherally-acting drugs, it outlines ex vivo phrenic nerve-diaphragm and sciatic nerve-gastrocnemius muscle preparations to assess muscle contraction responses. The rabbit head drop method evaluates centrally-acting drugs' abilities to relax neck muscles supporting the head.
This document discusses toxicity testing and provides details about various toxicity studies. It explains that toxicity testing involves observing adverse effects of chemicals in living organisms. It then describes different types of toxicity studies including acute, sub-acute, sub-chronic, chronic, and carcinogenicity studies. The document provides details about parameters evaluated in acute and chronic toxicity studies such as dosage, duration, symptoms observed, and endpoints. It also discusses alternative methods to traditional animal testing and guidelines for reporting toxicity study results.
Initial considerations for the study design include information on the test chemical's identity, properties, and results from previous toxicity tests. The guideline describes conducting a chronic toxicity study in rodents for 12 months, with the potential for interim kills and satellite groups. Key steps include dosing animals daily, observing them for signs of toxicity, and conducting clinical pathology, including hematology, clinical biochemistry, and urinalysis at various times. At the end, a full gross necropsy is performed and tissues are examined microscopically. Results are reported individually and summarized, including survival, body weights, food consumption, toxic responses, organ weights, and histopathological findings.
The document provides guidelines for testing chemicals for reproductive toxicity as outlined by the OECD. It discusses testing chemicals on both male and female rats to assess effects on fertility. For males, rats are dosed for a minimum of 4 weeks and examined for effects on testes and epididymides weight and histopathology as well as sperm motility and morphology. For females, rats are dosed throughout mating, pregnancy and lactation periods and assessed for effects on fertility, gestation, and offspring parameters. Clinical observations and pathology exams are also conducted.
The document provides guidelines for testing chemicals for reproductive toxicity as outlined by the OECD. It discusses testing chemicals on both male and female rats to assess effects on fertility. For males, rats are dosed for a minimum of 4 weeks and examined for effects on testes and epididymides weight and histopathology as well as sperm motility and morphology. For females, rats are dosed throughout mating, pregnancy and lactation periods and examined for effects on fertility, gestation, and offspring parameters. Clinical observations and pathology exams are also conducted.
This document provides an overview of acute toxicity studies and OECD test guidelines for assessing acute oral toxicity. It discusses the principles and procedures for acute oral toxicity fixed dose tests per OECD Guideline 420. Key points include:
- Guideline 420 is an alternative to the conventional acute toxicity test that uses fewer animals and causes less suffering
- It involves dosing groups of animals with fixed doses (e.g. 5, 50, 300, 2000 mg/kg) and observing any signs of toxicity or mortality
- A sighting study is conducted to determine the starting dose for the main study
- Multiple animals are tested at each dose level in the main study with observation periods to monitor for any toxic effects
General toxicology testing refers to a series of toxicity tests required by international regulators to prove safety in experimental animals prior to human testing. It includes acute, sub-acute, and chronic toxicity tests conducted according to OECD guidelines in rodents and non-rodents. Preclinical studies include phytochemistry, formulation development, pharmacology/pharmacokinetic profiling, safety toxicology studies, and efficacy studies. Toxicology studies are guided by regulatory requirements like OECD/ICH guidelines and Good Laboratory Practices to ensure quality. Acute, sub-acute, and chronic toxicity tests provide information on toxicity effects from single or repeated substance exposure over different time periods and help determine safe doses for clinical trials.
The guidelines describe about the subacute toxicity studies in rodents with a comparison with the previous guideline.it also includes the comparison of all three subacute toxicity studies OECD 407, OECD 410, and OECD 412
The document summarizes several OECD guidelines for dermal toxicity testing:
- Guideline 402 describes methods for acute dermal toxicity testing using rats. Animals are exposed to test chemicals at fixed doses and observed for 14 days.
- Guidelines 410, 411, and 434 describe methods for repeated dose dermal toxicity testing over 21/28 days, 90 days, and other durations to evaluate sub-chronic effects. Rats, rabbits or guinea pigs are exposed daily and observed for signs of toxicity.
- Guideline 435 describes an invitro membrane barrier method for evaluating skin corrosion potential without using live animals.
Pre-clinical screening involves testing potential new drugs in animal models before human trials to evaluate safety and efficacy. This includes pharmacological screening to determine mechanism of action and dose response, as well as toxicological testing to identify adverse effects and calculate safe starting doses for clinical trials. Studies progress from molecular and cellular assays to whole animal experiments. Acute and repeated dose toxicity tests are followed by sub-chronic and chronic studies to identify long-term effects. These pre-clinical studies aim to generate data required to deem a new compound safe enough for initial human testing.
This document outlines the principles and types of non-clinical toxicity studies conducted in animals prior to testing pharmaceuticals in humans. It discusses general principles like complying with Good Laboratory Practice, using standardized equipment and protocols. It also describes the different types of toxicology studies including toxicokinetic, reproductive toxicity, teratogenicity and perinatal studies. The goal is to assess safety and predict potential adverse effects in humans by administering test substances to animals and observing toxicity.
The document provides information on chronic toxicity studies as outlined in OECD Test Guideline 452. It discusses that chronic toxicity studies involve administering test substances to animals daily for over 90 days, typically 12 months, to identify target organs and dose-response relationships. The test substance is given orally, dermally, or via inhalation to groups of rodents like rats or mice, with at least 20 animals of each sex per dose group. Animals are observed closely for signs of toxicity and may be killed at interim periods or after 12 months for examination.
This document discusses various types of animal toxicity studies that are required before a drug can be administered to humans. It describes how these studies help establish the therapeutic index and predict adverse effects in humans. The key types of studies mentioned are systemic toxicity studies (including single dose, repeated dose, reproductive, and local toxicity), allergenicity/hypersensitivity studies, genotoxicity studies, and carcinogenicity/oncogenicity studies. Each type of study has specific objectives, test models used, parameters evaluated, and methods for conducting the studies and evaluating results. The studies aim to assess benefits and risks of drugs and establish their safety profiles before human use.
The document discusses various stages of drug development from preclinical to clinical trials in animals and humans. It describes studies conducted to determine toxicity, therapeutic index, adverse effects, and safety of new drug candidates. These include studies to evaluate single and repeated dose toxicity, reproductive toxicity, local toxicity, genotoxicity, and carcinogenicity. The goal is to accurately predict a drug's effects in humans based on animal studies and ensure safety before clinical trials.
chronic dermal and inhalational studies as per OECDSohil Shah
This document presents guidelines for chronic toxicity studies as outlined by the OECD. It discusses the objectives of chronic toxicity studies which are to identify hazardous properties, target organs, dose responses, and predict chronic effects in humans. It describes principles such as administering test substances daily to rodents for 12 months to observe toxicity. It provides details on housing, feeding conditions, procedures, observations, and reporting of results for chronic dermal and inhalation studies.
This document discusses teratogenicity studies, which assess the ability of substances to cause birth defects. It covers the mechanisms, principles, types of studies, observations, data reporting, and evaluation. Regarding study types, it describes single generational studies under FDA guidelines to evaluate effects on fertility and reproductive performance. Segment II assesses developmental toxicity by exposing pregnant rats to the test substance from days 6-15 of gestation, then examining fetuses for abnormalities on day 20. The document provides details on study procedures, observations, and reporting of results to evaluate if the substance is teratogenic.
Subacute toxicity testing is conducted over 28 days to estimate safety margins of substances. It involves exposing test animals like rats to substances via oral, dermal or inhalation routes and observing for signs of toxicity. Key guidelines for subacute toxicity testing are OECD 407 for oral exposure, OECD 410 for dermal exposure, and OECD 412 for inhalation exposure. These studies provide important toxicity data used in chemical risk assessments.
GENERAL GUIDELINES FOR TOXICOPATHOLOGY STUDYRahul Kadam
The nonclinical safety study recommendations for the marketing approval
of a pharmaceutical usually include single and repeated dose toxicity
studies, reproduction toxicity studies, genotoxicity studies, local tolerance
studies, and for drugs that have special cause for concern or are intended
for a long duration of use, an assessment of carcinogenic potential. Other
nonclinical studies include pharmacology studies for safety assessment
(safety pharmacology) and pharmacokinetic (absorption, distribution,
metabolism, and excretion (ADME)) studies. These types of studies and
their relation to the conduct of human clinical trials are presented in this
guidance.
This document discusses teratogenicity studies and provides details on how to conduct prenatal developmental toxicity tests according to OECD Guideline 414. It defines key terms like teratogen and teratology. Historical teratogens like thalidomide, Accutane, DES, and alcohol are described along with their effects. The FDA pregnancy drug categories and critical periods of development are outlined. Test procedures include selecting animal species, housing, dosing, observations, post-mortem examinations of dams and fetuses, and results reporting. The goal is to identify effects of substances on prenatal development and discriminate between general toxicity and developmental toxicity.
This document discusses drugs used to treat helminthiasis (intestinal worm infections). It begins by defining helminthiasis and describing the clinical symptoms. It then classifies the main types of intestinal worms as nematodes (roundworms) and platyhelminthes (flatworms such as tapeworms). Various anti-helminthic drug classes are discussed, including benzimidazoles (e.g. albendazole, mebendazole), pyrantel pamoate, diethyl carbamazine, ivermectin, levamisole, niclosamide, and praziquantel. Specific drugs like mebendazole, albendazole
This document discusses various antifungal drugs and their mechanisms of action. It describes Amphotericin B as a polyene antibiotic that binds to ergosterol in fungal cell membranes to form pores, and Griseofulvin as a heterocyclic benzofuran that disorients fungal microtubules. Key classes of antifungal agents are defined, and the pharmacology and uses of Amphotericin B and Griseofulvin are explained in detail.
This document discusses macrolide antibiotics. It describes their mechanism of action as inhibiting protein synthesis by binding to the 50s ribosomal subunit. It outlines their pharmacokinetics, noting their absorption in the small intestine and distribution to tissues like the tonsils, lungs, and prostate. The document concludes by explaining the clinical uses of macrolides for treating respiratory, neonatal, and genital infections caused by bacteria like streptococcus and chlamydia.
This document discusses aminoglycoside antibiotics. It describes their mechanism of action as inhibiting protein synthesis by binding to bacterial ribosomes. It outlines their pharmacokinetics, including that they are not absorbed orally and are administered via injection. It also covers their uses for treating various bacterial infections like tuberculosis, UTIs, and pneumonia.
Growth hormone is a single chain peptide hormone that promotes growth in children and maintains protein synthesis, fat metabolism, and glucose regulation in adults. It acts through insulin-like growth factors to exert its effects. Conditions of excessive or deficient growth hormone levels can cause gigantism or dwarfism respectively. Growth hormone secretion is regulated by growth hormone-releasing hormone and somatostatin, while its effects are mediated by insulin-like growth factors. Prolactin similarly regulates breast development and lactation. Hyperprolactinemia can result from tumors or drugs and cause issues like galactorrhea or infertility.
ICH guidelines provide standards for toxicity studies to ensure safe, effective, and high quality pharmaceutical products. Guideline S3A deals with conducting toxicity studies and quantifying exposure. General principles include quantifying exposure levels in different species and sexes using plasma concentration or area under the curve. Toxicokinetic studies should be performed to determine metabolite levels and justify dose levels. Reporting should include detailed toxicokinetic data and evaluation. Toxicokinetics are assessed in various toxicity studies including single dose studies, repeated dose studies, genotoxicity studies, carcinogenicity studies, and reproductive toxicity studies.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. Contents
1) Introduction
2) Description of the methods
Pilot studies
Animal Selection
Test substance
Dose selection
Administration of test substance
Measurements
Time Course Studies
3) Supplemental Approaches
4) Data & Reporting
3. INTRODUCTION
OECD : Organisation for Economic Co-Operation & Development
Headquarter: Paris, France
Guideline No: 417 for toxicity studies, adopted on 22 July, 2010
Purpose: to obtain adequate info on ADME, to aid in relating concentration or dose to
observed toxicity, to aid in understanding its mechanism of toxicity
Not designed to special circumstances such as pregnant or lactating women & offspring
Total 115 guidelines for toxicity studies
4. OECD 402 – Acute Dermal Toxicity
OECD 404 – Acute Dermal Irritation/Corrosion
OECD 406 – Skin Sensitization
OECD 407 – Repeated Dose 28-day Oral Toxicity Study in Rodents
OECD 408 – Repeated Dose 90-Day Oral Toxicity Study in Rodents
OECD 410 – Repeated Dose Dermal Toxicity: 21/28-day Study
OECD 411 – Sub-chronic Dermal Toxicity: 90-day Study
OECD 414 – Prenatal Development Toxicity Study
OECD 415 – One-Generation Reproduction Toxicity Study
OECD 416 – Two-Generation Reproduction Toxicity
OECD 420 – Acute Oral Toxicity – Fixed Dose Procedure
OECD 421 – Reproduction/Developmental Toxicity Screening Test
OECD 422 – Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity
Screening Test
OECD 423 – Acute Oral toxicity – Acute Toxic Class Method
OECD 425 – Acute Oral Toxicity: Up-and-Down Procedure
OECD 427 – Skin Absorption: In Vivo Method
OECD 429 – Skin Sensitization: Local Lymph Node Assay
OECD 442 A/B – Skin Sensitization
OECD 443 – Extended One-Generation Reproductive Toxicity Study
OECD 451 – Carcinogenicity Studies
OECD 452 – Chronic Toxicity Studies
OECD 453 – Combined Chronic Toxicity/Carcinogenicity Studies
5. Toxicity type Animal Procedure Observation
Acute Oral Toxicity Rat Fasted 3-4 hr before
test, oral administration
by gavage using a
stomach tube or a
suitable cannula
1 mL/100 g body
weight for 14 days
Changes in skin & fur,
eyes & mucous
membranes. Tremors,
convulsions, salivation,
diarrhea, lethargy,
& coma
Acute Dermal Toxicity Rat Test subs (200 mg/kg)
applied to skin by
removing fur (10 %
body weight), held with
gauge dressing for 24
hour
Changes in skin & fur,
eyes & mucous
membranes. Tremors,
convulsions, salivation,
diarrhea, lethargy,
& coma
6. Skin
Sensitization
Test
Guinea pig Animals (5) exposed to test
substance by intradermal
injection or epidermal
application, following a rest
period of 10-14 days, animals
are exposed to a challenge
dose
Extent & degree of skin reaction
in test animals compared to
control animals
Acute eye
irritation
Albino rabbit 60 mins prior to test substance,
buprenorphine 0.01 mg/kg
administered by s.c. route to
provide therapeutic level of
systemic analgesia & eye not
washed for 24 hour
Ocular lesion, corneal ulceration,
corneal opacity, absence of light
reflex, ulceration of conjunctival
membrane (at 21 days or any
time when pain observed)
7. Inhalation toxicity Rat Inhalation chamber
5 mg/L for aerosols
20 mg/L for vapours &
20,000 ppm for gases
All body organs necropsed
including brain, heart, kidneys,
liver, lung, spleen, ovaries, testes
Reproduction/De
velopmental
toxicity screening
test
Rat Administration by gavage
daily for 7 days a week, 1
ml/100 g body wt.
Dosing begin at 2 weeks
prior to mating
Body wt, blood samples, gross
necropsy
8. Carcinogenicit
y Studies
Rat Orally by gavage in diet or
drinking water, NMT 5 % of
total diet, dosed daily for 24
months
Body wt., tumour dev,
Haematology, gross necropsy
Prenatal
Development
al Toxicity
Study
Rat or Rabbit Daily from 5 days post mating,
orally 1000 mg/kg body wt.
Mortality, moribundity, pertinent
behavioral changes & all signs of
overt toxicity observed by killing
females one day prior to delivery
The fetuses is also examined
9. One generation
reproduction
toxicity study
Rat/mouse Test substance to both sexes
during mating period & only
to females during pregnancy
& nursing period in
diet/drinking water,
1000 mg/kg, 2 weeks prior to
mating, upto 3 week mating
period
Behavioral changes, signs of
toxicity, mortality, body wt,
gross necropsy
Neurotoxicity study
in rodents
Rat Oral by gavage in
diet/drinking water, 1000
mg/kg body wt, dosed daily
for 28 days
Neurological abnormalities,
Haematology, body wt,
ophthalmic evaluation,
histopathology
10. Genetic
Toxicology:
Rodent
Dominant
Lethal Test
Rat/Mice Males are exposed to test
substance & mated to
untreated virgin females, single
administration of test substance
by oral or intraperitoneal
injection
Females are sacrificed & contents of
uteric are examined to determine
number of implants & live & dead
embryos.
Calculation of dominant lethal effect
is based on comparison of live
implants per female in treated group
to live implants per female in the
control group
Bacterial
Reverse
Mutation Test
Bacteria Cultures of bacteria are grown,
at least 5 strains of bacteria, 4
species of S. typhimurium & an
E coli.
Bacteria is exposed to test
substance & incubated at 37 C
for 48-72 hr & number of
revertant colonies is counted
Signs of toxicity, sign of precipitation,
individual plate counts, mean
number of revertant colonies per
plate & std deviation
11. DESCRIPTION OF THE METHODS
1) Pilot Studies
2) Animal Selection
a) Age & Strain
Young, adult animals of same age, weight variation ±20%
b) Number & Sex of animals
4 animals of same sex, both sexes if sex-related differences in toxicity
c) Housing & Feeding Conditions
Housed individually in artificial light, temp 22 degree C, relative humidity 30-70 %
3) Test Substance
Radiolabelled test substance 14C for mass balance & metabolite identification
Unlabelled if specificity & sensitivity is high & mass balance and metabolite identification
can be evaluated
12. 4) Dose Selection
Pilot Study
Single oral dose, dose should be non-toxic, high enough to allow for metabolite
identification in excreta
Main studies
Minimum of two doses
substance of low toxicity, maximum dose of 1000 mg/kg body weight
5) Administration of Test Substance
Dissolved or suspended in the appropriate vehicle
maximum volume administered depends on size of test animals, not exceeding 10mL/kg
body weight for rodents.
Vehicle for IV not interfere with blood integrity or blood flow
Anaesthesia should be used if one cannulates the jugular vein
13. 6) Measurements
Mass Balance
Sum of percent of dose excreted & present in tissues
Absorption
Amount absorbed is Mass balance - % dose in GIT + faeces
In biliary excretion, bile ducts of at least four animals cannulated & single dose of test
administered
Percent absorption = (amount in bile + urine + expired air + carcass without GI tract
contents)/amount administered * 100
Bioavailability
F = ( AUCexp / AUC iv) * (Dose iv / Dose ip)
Exp is experimental route (oral, dermal or inhalation)
14. Tissue Distribution
% of total drug in tissue measured at termination of excretion experiment
if no substance detected, tissue distribution be measured at peak plasma concentration
Tissues collected include liver, GI tract, kidney, spleen, whole blood, target organ tissues
other tissues (e.g. thyroid, erythrocytes, reproductive organs, skin, eye
Organ dissection, homogenization, combustion, autoradiography, etc
Metabolism
Excreta collection for identifying metabolites, 5 % or greater of administered dose
Identification i.e. structural determination of components
15. Excretion
determined by % recovered from urine, faeces & expired air at appropriate time intervals
Collection of excreta terminated at 7 days or after 90 % of the administered dose has
recovered
Sampling at 6, 12 & 24 hour
7) Time Course Studies
Plasma/Blood Kinetics
Cmax, Tmax, half life, AUC; studies to be conducted at 2 or more doses
4 animals of one sex per dose group, different sex if sex-related differences
Blood samples at suitable time points
16. Enzyme Induction/ Inhibition studies in
a) Relationship between biotransformation of test substance & enhanced toxicity
b) Non-linear relationship data between dose & metabolism
c) Toxic metabolite produced by enzyme pathway
SUPPLEMENTAL APPROACHES
provides info about ADME of a chemical in certain species
Use of in-vitro information
Freshly isolated or cultured hepatocytes and subcellular fractions (e.g. microsomes,
from liver used to study metabolites.
Studies with microsomes useful to address potential gender and life-stage differences
17. Use of Toxicokinetic data from Toxicity studies
Analysis of blood, tissue, excreta samples provides data on
bioavailability
changes in plasma concentration in time (AUC, Cmax)
Bioaccumulation potential
Clearance rates
Gender or life-stage changes
Age-related sensitivity due difference in blood-brain barrier
Sub population sensitivity due difference in biotransformation
Extent of exposure of fetuses by transplacental transfer of chemicals
Use of Toxicokinetic Modeling
a) partition coefficients
b) biochemical constants and physiological parameters
c) route-specific absorption parameters
d) in vivo kinetic data for model evaluation
18. DATA & REPORTING
Study report including
Summary
Study design & description of method used
Also mass balance, nature & magnitude of metabolites, tissue residue, rate of clearance,
bioaccumulation potential
Introduction
Study objective, rationale and design, appropriate references, any background history
Materials & Methods
a) Test Substance
Identification by chemical name, chemical purity, physical state, colour, solubility, partition
coefficient, stability, corrosivity, information on isomers
Description of any vehicle, diluents, suspending agents, emulsifiers or other materials
19. b) Test Animals
Species, strain, age, sex, body weight, health status
c) Methods: It includes
Justification for selection of dose levels;
Description of pilot studies used in the experimental design of the follow-up studies;
How the dosing solution was prepared and the type of solvent or vehicle, if any, used;
Number of treatment groups and number of animals per group;
Dosage levels and volume (and specific activity of the dose when radioactivity is used);
Route(s) and methods of administration;
Frequency of dosing;
Fasting period (if used);
Animal handling;
Sample collection and handling;
Analytical methods used for separation, quantitation and identification of metabolites;
20. d) Statistical Analysis
info on method of analysis and computer program
Results
graphic illustrations of the findings,
reproduction of representative chromatographic and spectrometric data,
metabolite identification/quantification and proposed metabolic pathways
molecular structure of metabolites.
Discussion and Conclusion
Provide a proposed metabolic pathway based on the results of the metabolism and disposition of the
test substance;
Discuss any potential species and sex differences regarding the disposition and/or biotransformation
of the test substance;
Tabulate and discuss the identification and magnitude of metabolites, rates of clearance,
bioaccumulation potential, and level of tissue residues of parent, and/or metabolite(s), as well as
possible dose-dependent changes in TK parameters, as appropriate;
Provide a concise conclusion that can be supported by the findings of the study;