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.
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
ICH is the “International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for
Human Use”
ICH is a joint initiative involving both regulators and research based industry representatives of the EU, Japan and the US in
scientific and technical discussions of the testing procedures required
to assess and ensure the safety, quality and efficacy of medicines
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
ICH is the “International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for
Human Use”
ICH is a joint initiative involving both regulators and research based industry representatives of the EU, Japan and the US in
scientific and technical discussions of the testing procedures required
to assess and ensure the safety, quality and efficacy of medicines
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
Toxicity is the science dealing with properties, action, toxicity, fatal dose detection or interpretation of result of toxicological analysis & treatment of poison.
Toxicity studies helps to avoid adverse effect and enhance the safety of drug.
This slide provides the information about toxicity screening on experimental animals.
Acute eye irritation test as per OECD guidelinesmadhvi Chaubey
toxicological testing studies as per OECD guidline.
Toxicology is the branch of biology, chemistry and medicine concerned with the study of the adverse effects of chemicals on living organisms.
As per OECD test no. 405 : acute eye irritation test should be done as according to the procedure mentioned under guideline's section.
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
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
Toxicity is the science dealing with properties, action, toxicity, fatal dose detection or interpretation of result of toxicological analysis & treatment of poison.
Toxicity studies helps to avoid adverse effect and enhance the safety of drug.
This slide provides the information about toxicity screening on experimental animals.
Acute eye irritation test as per OECD guidelinesmadhvi Chaubey
toxicological testing studies as per OECD guidline.
Toxicology is the branch of biology, chemistry and medicine concerned with the study of the adverse effects of chemicals on living organisms.
As per OECD test no. 405 : acute eye irritation test should be done as according to the procedure mentioned under guideline's section.
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 Organization for Economical and Co-operation Development was used for testing of chemicals.
The original OECD guideline 451 for carcinogenecity study was adopted in 1981.
A Major carcinogenicity study is done on rodents
Mainly there routes of administration: oral, dermal, and inhalation.
OECD Test Guideline 420: Acute Oral Toxicity - Fixed Dosepp_shivgunde
OECD Test Guideline 420: Acute Oral Toxicity - Fixed Dose
Guideline 420 was adopted in July 1992 as the first alternative to the conventional acute toxicity test.
The identification of the carcinogenic properties of a chemical, resulting in an increased incidence of neoplasms, increased proportion of malignant neoplasms or a reduction in the time to appearance of neoplasms, compared with concurrent control groups.
The identification of target organ(s) of carcinogenicity.
The identification of the time to appearance of neoplasms.
Characterisation of the tumour dose-response relationship.
Similar to chronic dermal and inhalational studies as per OECD (20)
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
Contact ME {89011**83002} Haridwar ℂall Girls By Full Service Call Girl In Ha...
chronic dermal and inhalational studies as per OECD
1. Chronic, dermal and inhalational studies as per
OECD Guidelines
Presented by,
Sohil shah
M. Pharmacy 1st year
Pharmacology
2. Content
Introduction
Objectives of chronic toxicity study
principle
Selection of animal species
Housing and feeding conditions
Procedure
Obsrvation
Test report
references
3. TOXICITY STUDIES - INTRODUCTION
• Toxicology classically has been defined as the study of poisons & concerned with the
adverse effects of xenobiotics.
• Casarett 1996 defined it as a science that defines the limits of safety of chemical
agents for human & animal populations.
• Toxicological screening is very important for the development of new drugs and for the
extension of the therapeutic potential of existing molecules.
• The US-FDA states that it is essential to screen new molecules for pharmacological
activity and toxicity potential in animals (21CFR Part 314).
• Toxicity tests are mostly used to examine specific adverse events or specific end
points such as cancer, cardiotoxicity, and skin/eye irritation.
• Toxicity testing also helps calculate the No Observed Adverse Effect Level
(NOAEL)
dose and is helpful for clinical trails.
4. Cont..
OECD provide certain guidelines for chronic toxicity studies
The origin guideline 452 was adopted in 1981
The majority of toxic studies are carried out in rodent species
For chronic toxicity study oral, dermal and inhalational route is preferred
The choice of route of administration depends on the physical and chemical
characteristics of the test compound
5. Objectives
Identification of hazardous properties of a chemical
Identification of target organ
Characterization of dose response relationship
The prediction of chronic toxicity effect at human exposure level
6. Principle
The test substance is administered daily in a graduated dose to saveral groups of
experimental animal for a period of 12th month although longer or shorter
duration may also be chosen
During this period of alleviation the animals are observed closely for sign of
toxicity
7. Selection of species
For the chronic toxicity studies generally rodents species are used
Like rat and mice
Rat and mice have been preferred experimental model because of their relatively
short life span
Young healthy adult animals of commonly used laboratory strains should be
employed
The chronic toxicity study should be carried out in animals from the same strain
and source as those used in preliminary toxicity study(ies) of shorter duration.
8. Housing and feeding conditions
Animals may be housed individually, or be caged in small groups of the same sex;
individual housing should be considered only if scientifically justified
The temperature in the experimental animal room should be 22’C (± 3’C).
humidity should be at least 30% and preferably not exceed 70%
Lighting should be artificial, the sequence being 12 hours light, 12 hours dark.
For feeding, conventional laboratory diets may be used with an unlimited supply
of drinking water.
heavy metals and mycotoxins, that might influence the outcome of the test, should
be as low as possible .
9. Preparation of animal
Healthy animals, which have been acclimated to laboratory conditions for at least
7 days and have not been subjected to previous experimental procedures, should
be used.
the weight variation of animals used should be minimal and not exceed ± 20 % of
the mean weight of all the animals within the study
Animals should be randomly assigned to the control and treatment groups
After randomisation, there should be no significant differences in mean body
weights between groups within each sex
10. Procedure
Number and sex of animals :-
Both sexes should be used.
A sufficient number of animals should be used so that at the end of the study
enough animals in every group are available for thorough biological and statistical
evaluation
Normally, at least 20 animals per sex per group should be used at each dose level
11. Cont…
Dose group and dosage :-
At least three dose levels and a concurrent control should be used,
Dose levels will generally be based on the results of shorter-term repeated dose or
range finding studies and should take into account any existing toxicological and
toxicokinetic data available for the test substance or related materials.
The top dose should not exceed 1000 mg/kg body weight/day
The control group shall be an untreated group or a vehicle-control group if a
vehicle is used in administering the test substance
12. Cont…
Preparation of doses and administration of test substance:-
The test substance is normally administered by inhalational route or by dermal
route
The route and method of administration is dependent on the purpose of the study,
the physical/chemical properties of the test substance, its bioavailability and the
predominant route and method of exposure of humans.
In case of dermal administration, the animals are dosed with the test substance
daily (seven days each week), normally for a period of 1 year
Dosing by the inhalation route is carried out for 6 hours per day, 5 days per week.
13. Cont…
Duration of study:-
While this Test Guideline primarily is designed as a 12 month chronic toxicity
study, the study design also allows for and can be applied to either shorter (e.g. 6
or 9 months) or longer (e.g., 18 or 24 months) duration studies, depending on the
requirements of particular regulatory regimes or for specific mechanistic
purposes.
14. Observations
All animals should be checked for morbidity or mortality and for specific signs of
toxicological relevance, in particular for neurofunctional and neurobehavioural
signs
Signs noted should include, but not be limited to, changes in skin, fur, eyes,
mucous membranes, occurrence of secretions and excretions and autonomic
activity (e.g., lacrimation, piloerection, pupil size, unusual respiratory pattern).
Changes in gait, posture and response to handling as well as the presence of clonic
or tonic movements, stereotypies (e.g., excessive grooming, repetitive circling) or
bizarre behavior (e.g., self-mutilation, walking backwards) should also be
recorded
15. Body weight, food/water consumption and food
efficiency
All animals should be weighed at the start of treatment, at least once a week for
the first 13 weeks, and at least monthly thereafter.
Measurements of food consumption and food efficiency should be made at least
weekly for the first 13 weeks and at least monthly thereafter.
Water consumption should also be considered for studies in which drinking
activity is altered and should be measured at least weekly for the first 13 weeks
and at least monthly thereafter, when the substance is administered in drinking
water.
16. Test report
The test report should include the following information :-
Test substance :-
physical nature, purity, and physicochemical properties;
identification data;
source of substance;
batch number
Vehicle (if appropriate):
justification for choice of vehicle (if other than water
17. Cont..
Test animals:
species/strain used and justification for choice made;
number, age, and sex of animals at start of test;
source, housing conditions, diet, etc.;
individual weights of animals at the start of the test
18. Cont..
Test conditions:
rationale for route of administration and dose selection;
when applicable, the statistical methods used to analyse the data;
details of test substance formulation/diet preparation, achieved concentration,
stability and homogeneity of the preparation;
route of administration and details of the administration of the test substance;
for inhalation studies, whether nose only or whole body;
actual doses (mg/kg body weight/day), and conversion factor from diet/drinking
water test substance concentration (mg/kg or ppm) to the actual dose, if applicable;
details of food and water quality
19. Cont..
Results:
survival data;
body weight/body weight changes;
food consumption, calculations of food efficiency, if made, and water consumption
if applicable;
toxic response data by sex and dose level, including signs of toxicity;
nature, incidence (and, if scored, severity), and duration of clinical observations
((whether transitory or permanent);
ophthalmological examination;
haematological tests;
20. Cont..
Results:
clinical biochemistry tests;
urinalysis tests;
outcome of any investigations of neurotoxicity or immunotoxicity
terminal body weight;
organ weights (and their ratios, if applicable);
necropsy findings;
a detailed description of all treatment-related histopathological findings;
absorption data if available
21. references
DRAFT OECD GUIDELINE FOR THE TESTING OF CHEMICALS
Test Guideline 452: Chronic Toxicity Studies.