This document contains notes on principles of animal toxicology from Ramdas Bhat of Srinivas College of Pharmacy. It discusses the types of preclinical toxicity studies done on pharmaceutical products, including acute, sub-acute, and chronic toxicity studies. It provides details on acute toxicity studies, how LD50 is determined, and guidelines from the Organization for Economic Cooperation and Development for standardized toxicology testing.

1. PHARMACOLOGY NOTES
RAMDAS BHAT
SRINIVAS COLLEGE OF PHARMACY 1
PRINCIPLES OF ANIMAL
TOXICOLOGY: ACUTE, SUB-
ACUTE AND CHRONIC
TOXICITY
Prepared by,
RAMDAS BHAT (M.Pharm)
Asst. Professor
Srinivas College of Pharmacy
Mangalore
7795772463
Ramdas21@gmail.com

2. PHARMACOLOGY NOTES
RAMDAS BHAT
SRINIVAS COLLEGE OF PHARMACY 2
• Pharmaceutical products must undergo a battery of preclinical general toxicology studies
to provide information regarding the safety of a potential new drug prior to initiation of the
various clinical trials in humans, which are necessary before a molecule can become an
approved drug.
• The order of the general toxicology studies begins with acute screening and progresses
through longer durations of exposure up to as much as 1 year in length.
• In this chapter, numerous regional and global considerations regarding the influence
rendered on the types of general toxicology study designs needed for regulatory submission
are discussed.
• This chapter also covers how to integrate general toxicology assessments into the
preclinical program.
• By understanding the intricacies of the general toxicology plan, the hope is that it will
facilitate smoother transitions as the potential drug candidate moves forward in
development.
PRECLINICAL STUDIES
• After synthesizing/identifying a prospective compound, it is tested on animals to expose
the whole pharmacological profile.
• Experiments are generally performed on a rodent (mouse, rat, guinea pig, hamster, rabbit)
and then on a larger animal (cat, dog, monkey).
• As the evaluation progresses unfavorable compounds get rejected at each step, so that only
a few out of thousands reach the stage when administration to man is considered.
Types of tests:
1. Screening tests: These are simple and rapidly performed tests to indicate presence or
absence of a particular pharmacodynamic activity. e.g., analgesic or hypoglycemic activity.
2. Tests on isolated organs, bacterial cultures, etc: Preliminary tests to detect specific
activity, such as antihistaminic, antisecretory, vasodilator, antibacterial, etc.
3. Tests on animal models of human disease: Such as seizures in rats, spontaneously
(genetically) hypertensive rats, experimental tuberculosis in mouse, alloxan induced
diabetes in rat or dog etc.
4. 4. General observation tests: The drug is administered in tripling doses to profile of
effects small groups of mice and are observed for overt effects. Preliminary clues are drawn
from the observed.
5. Confirmatory tests and analogous activities: Compounds found active are taken up for
detailed study by more elaborate tests which confirm and characterize the activity. Other
related activities: e.g., antipyretic and anti-inflammatory activity in an analgesic is tested.
6. Mechanism of drug action: Eg: Whether an antihypertensive is an α blocker or β blocker
7. Systemic pharmacology: Effects on major organ systems such as nervous, cardiovascular,
respiratory, renal, g.i.t are worked out.
TOXICOLOGY

3. PHARMACOLOGY NOTES
RAMDAS BHAT
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8. Quantitative tests: The dose-response relationship, maximal effect and comparative
potency/efficacy with existing drugs is ascertained.
9. Pharmacokinetics: The absorption, tissue distribution, metabolism, excretion, volume of
distribution and half-life are quantified.
10. Toxicity tests: The aim is to determine safety of the compound in at least 2 animals such
as mice, rats and dogs.
ACUTE TOXICITY STUDIES
• Acute toxicity refers to the adverse effects that result from a single exposure to a substance
or mixture, or multiple exposures within a short period, such as 24 hours.
• It is typically measured by determining the dose of a substance that causes adverse effects
in a test animal or human subject.
• Acute toxicity is important to evaluate for regulatory purposes because it helps to determine
the potential hazards of a substance and to establish safe exposure limits.
• The severity of acute toxicity can vary widely depending on the substance, the dose, and
the route of exposure.
• Common routes of exposure include ingestion, inhalation, and dermal contact.
• Ingestion is the most common route of exposure, particularly for children who may
accidentally ingest substances.
• Inhalation can occur in occupational settings, during transportation of hazardous materials,
or during accidental releases of toxic gases.
• Dermal contact can occur in workplace settings, during the use of consumer products, or
during spills of toxic liquids.
• Acute toxicity can result in a range of adverse effects, including nausea, vomiting, diarrhea,
headaches, dizziness, seizures, respiratory failure, and even death.
• The severity of these effects depends on the dose of the substance, the duration of exposure,
and the susceptibility of the exposed individual.
• Some individuals may be more vulnerable to acute toxicity due to pre-existing health
conditions, age, or other factors.
• To evaluate acute toxicity, regulatory agencies typically use animal testing to determine the
LD50 (the dose of a substance that is lethal to 50% of test animals).
• However, there is increasing interest in using non-animal methods for acute toxicity testing,
such as in vitro assays and computational models.
LD50 (LETHAL DOSE 50)
• LD50 (Lethal Dose 50%) is a measure of acute toxicity that indicates the dose of a
substance or chemical that is expected to cause death in 50% of test animals exposed to it.
• The LD50 value is typically expressed as milligrams of substance per kilogram of body
weight of the test animal.
• The LD50 is an important parameter used by regulatory agencies to determine the potential
hazard of a substance and to establish safe exposure limits for humans and the environment.
• The LD50 is used to classify substances into toxicity categories, such as "highly toxic,"
"moderately toxic," or "slightly toxic," based on the dose required to cause death in test
animals.
• The LD50 value is determined through animal testing, where a range of doses of a substance
is administered to a group of animals, typically rodents such as rats or mice.
• The animals are monitored for signs of toxicity, such as changes in behavior, body weight,
and mortality.

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SRINIVAS COLLEGE OF PHARMACY 4
• The dose that results in death in 50% of the animals is then determined as the LD50.
• It is important to note that the LD50 value is not a precise measure of toxicity, as it can
vary widely depending on the species, strain, age, and sex of the test animal, as well as the
route of exposure and other factors.
• Additionally, the LD50 test can cause pain and suffering to animals, and there are ethical
concerns about the use of animals in toxicity testing.
• As a result, there has been increasing interest in developing alternative methods for toxicity
testing that do not rely on animal testing, such as in vitro assays and computational models.
• These methods aim to provide more accurate, efficient, and humane methods for evaluating
the toxicity of substances.
OECD (ORGANIZATION FOR ECONOMIC COOPERATION AND DEVELOPMENT)
• The Organization for Economic Cooperation and Development (OECD) provides
guidelines for the testing of chemicals for their potential toxicity.
• The OECD Guidelines for the Testing of Chemicals provide a standardized approach for
the assessment of the toxicity of chemicals.
• These guidelines include methods for the testing of acute toxicity in various organisms,
including rats, mice, and rabbits.
• Here is a brief overview of some of the most commonly used OECD guidelines:
1. OECD Test Guideline 401: Acute Oral Toxicity. This guideline describes a method for
determining the acute oral toxicity of a test substance in rats.
2. OECD Test Guideline 402: Acute Dermal Toxicity. This guideline describes a method for
determining the acute dermal toxicity of a test substance in rats.
3. OECD Test Guideline 403: Acute Inhalation Toxicity. This guideline describes a method
for determining the acute inhalation toxicity of a test substance in rats.
4. OECD Test Guideline 404: Acute Dermal Irritation/Corrosion. This guideline describes a
method for determining the potential for a test substance to cause irritation or corrosion of
the skin in rabbits.
5. OECD Test Guideline 405: Acute Eye Irritation/Corrosion. This guideline describes a
method for determining the potential for a test substance to cause irritation or corrosion of
the eyes in rabbits.
6. OECD Test Guideline 406: Skin Sensitization. This guideline describes a method for
determining the potential of a test substance to cause an allergic skin reaction in mice or
guinea pigs.
7. OECD Test Guideline 407: Repeated Dose 28-Day Oral Toxicity Study in Rodents. This
guideline describes a method for evaluating the sub chronic toxicity of a test substance in
rats or mice.
8. OECD Test Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents. This
guideline describes a method for evaluating the sub chronic toxicity of a test substance in
rats or mice over a longer duration.

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9. OECD Test Guideline 410: Repeated Dose Dermal Toxicity: 21/28-Day Study. This
guideline describes a method for evaluating the sub chronic dermal toxicity of a test
substance in rats.
10. OECD Test Guideline 414: Prenatal Developmental Toxicity Study. This guideline
describes a method for evaluating the potential of a test substance to cause developmental
toxicity in rats or rabbits.
11. OECD Test Guideline 421: Reproduction/Developmental Toxicity Screening Test. This
guideline describes a method for evaluating the potential of a test substance to cause
developmental toxicity and reproductive effects in rats.
12. OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test. This guideline describes a method
for evaluating the potential of a test substance to cause both repeated dose toxicity and
developmental toxicity and reproductive effects in rats.
13. OECD Test Guideline 425: This guideline provides a standard procedure for the testing
of chemicals to determine their acute oral toxicity.
14. OECD Test Guideline 471: Bacterial Reverse Mutation Test. This guideline describes a
method for evaluating the potential of a test substance to cause genetic damage in bacteria.
15. OECD Test Guideline 487: In Vitro Mammalian Cell Micronucleus Test. This guideline
describes a method for evaluating the potential of a test substance to cause chromosomal
damage in mammalian cells.
ADVANTAGES OF ACUTE TOXICITY:
1. Provides preliminary information: Acute toxicity studies can provide preliminary
information about the potential harmful effects of a substance. This can help in identifying
the need for further testing or in informing decisions about regulatory action.
2. Fast results: Acute toxicity studies can provide results in a relatively short period of time,
usually within a few days to a few weeks. This can be useful when quick decisions need to
be made about the potential risks of a substance.
3. Easy to conduct: Acute toxicity studies are generally simpler and less expensive to conduct
than sub chronic or chronic toxicity studies, which require longer testing periods and more
resources.
4. Can identify target organs: Acute toxicity studies can provide information about the
specific organs or systems that are most affected by a substance. This can help in identifying
the mechanisms of toxicity and in developing targeted interventions.
5. Provides dose-response data: Acute toxicity studies can provide dose-response data that
can be used to determine the LD50 and other toxicological parameters. This information
can be used to establish safe exposure levels for workers and the general public.
6. Useful for hazard classification: Acute toxicity studies are often used to classify substances
according to their hazard potential. For example, the Globally Harmonized System of
Classification and Labelling of Chemicals (GHS) uses acute toxicity data to assign
substances to one of four hazard categories based on their LD50 values.
7. Required by regulations: Acute toxicity studies are often required by regulatory agencies
as part of the risk assessment process for new and existing substances. The results of these

6. PHARMACOLOGY NOTES
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SRINIVAS COLLEGE OF PHARMACY 6
studies are used to inform decisions about the safety of a substance and to establish
exposure limits.
DISADVANTAGES OF ACUTE TOXICITY:
1. Limited exposure duration: Acute toxicity testing involves single or short-term exposures,
which may not reflect the effects of repeated or chronic exposure. Therefore, it may not
provide a complete picture of the potential risks associated with long-term exposure to a
substance.
2. Limited information on mechanisms of toxicity: Acute toxicity testing provides
information on the immediate effects of a substance but does not provide detailed
information on the mechanisms of toxicity. Sub chronic or chronic toxicity testing is needed
to provide more comprehensive information on the toxicological effects of a substance.
3. Limited evaluation of sublethal effects: Acute toxicity testing is primarily focused on lethal
effects, and may not detect sublethal effects that could be significant, particularly in the
long term. These effects can include changes in behavior, reproductive function, or immune
function.
4. Animal use and welfare concerns: Acute toxicity testing typically involves the use of large
numbers of animals, which raises ethical concerns about animal welfare. Many
organizations and regulatory agencies are working to reduce and replace animal testing,
particularly in cases where alternative testing methods are available.
5. Limited extrapolation to human exposure: Animal studies are not always predictive of
human response due to differences in physiology, metabolism, and susceptibility.
Therefore, the results of acute toxicity studies may not be directly applicable to human
exposures.
6. Limited information on environmental effects: Acute toxicity testing is typically conducted
on individual organisms in a laboratory setting and may not reflect the effects of a substance
on ecosystems or the environment.
SUBACUTE TOXICITY STUDIES
• Subacute toxicity studies are a type of preclinical toxicity testing that assess the potential
adverse effects of a substance over a period of several weeks or months.
• These studies are generally conducted in laboratory animals and are designed to evaluate
the effects of repeated exposure to a substance at sub-lethal doses.
• The results of subacute toxicity studies can provide important information about the
potential risks of a substance and can be used to establish safe exposure levels for humans
and the environment.
• Subacute toxicity studies typically involve the repeated administration of a substance to
laboratory animals over a period of 28 to 90 days, depending on the regulatory requirements
and the characteristics of the substance being tested.
• The animals are usually observed for signs of toxicity, changes in body weight, and
alterations in organ structure and function.
• Commonly used laboratory animals for subacute toxicity testing include rats, mice, dogs,
and non-human primates.
• In subacute toxicity testing, the substance is usually administered by the oral route, but
other routes of administration such as dermal or inhalation exposure can also be used.
• The doses used in subacute toxicity testing are usually lower than those used in acute
toxicity testing, but higher than those used in chronic toxicity testing.

7. PHARMACOLOGY NOTES
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SRINIVAS COLLEGE OF PHARMACY 7
• The doses are typically selected based on the results of acute toxicity testing and on
estimated human exposure levels.
• The endpoints measured in subacute toxicity testing may include clinical signs of toxicity,
hematological and biochemical parameters, histopathological changes, and changes in
organ weight.
• Additional endpoints may also be evaluated depending on the specific requirements of the
regulatory agencies.
• The results of subacute toxicity studies can be used to determine the no observed adverse
effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) of the
substance.
• These values can then be used to establish safe exposure levels for humans and the
environment.
• Additionally, subacute toxicity testing can also provide information on the target organs
and systems affected by the substance, the dose-response relationship, and the potential for
cumulative effects over time.
REQUIREMENTS:
• Dose selection: In a subacute toxicity study, the doses of the test substance are selected
based on the results of previous acute toxicity studies, as well as other relevant information
about the substance, such as its pharmacokinetics and toxicology profile. The goal is to
select doses that are high enough to detect any potential toxic effects, but low enough to
avoid severe or life-threatening toxicity.
• Route of administration: The route of administration in a subacute toxicity study is chosen
based on the intended use of the substance. For example, if the substance is intended for
oral consumption, it may be administered orally to the test animals. If the substance is
intended for topical use, it may be applied to the skin. If the substance is intended for
inhalation, it may be inhaled by the test animals.
• Monitoring: During a subacute toxicity study, the test animals are monitored for any
adverse effects, changes in health, weight, behavior, and organ function. This monitoring
may include daily observations, weekly weighings, and regular blood and urine analyses.
If any adverse effects are observed, the test animals may undergo additional evaluations,
such as histopathological examinations of the affected tissues.
• Statistical analysis: The results of a subacute toxicity study are analyzed statistically to
determine the dose-response relationship for the test substance. This allows for the
identification of the no observed adverse effect level (NOAEL), which is the highest dose
at which no adverse effects were observed. The NOAEL is used to help determine the safe
use and regulation of the substance.
• Regulatory considerations: The results of a subacute toxicity study may be used by
regulatory agencies, such as the U.S. Environmental Protection Agency (EPA) or the
European Chemicals Agency (ECHA), to make decisions about the safety and regulation
of the substance. For example, the EPA may use the results of a subacute toxicity study to
determine the safe use and labeling of a pesticide, or the ECHA may use the results to
evaluate the safety of a chemical for use in consumer products.

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RAMDAS BHAT
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EC50 and ED50 VALUE
• EC50 and ED50 are both dose-response metrics commonly used in toxicology and
pharmacology to assess the potency and effectiveness of a substance.
• EC50 is the concentration of a substance that is required to achieve 50% of the maximum
biological effect or response.
• It is typically used in in vitro studies and is measured in terms of the concentration of the
substance in a test system, such as a cell culture or enzyme assay.
• The lower the EC50 value, the more potent the substance is in eliciting the desired effect.
• ED50, on the other hand, is the dose of a substance that is required to achieve 50% of the
maximum biological effect or response.
• It is typically used in in vivo studies and is measured in terms of the dose of the substance
administered to the test animal.
• The lower the ED50 value, the more potent the substance is in eliciting the desired effect.
• In subacute toxicity testing, EC50 and ED50 values can be used to determine the optimal
dose of a substance for achieving the desired therapeutic or toxic effect.
• For example, in the development of a new drug, the EC50 value can be used to determine
the optimal dose for achieving the desired pharmacological effect while minimizing
toxicity.
• In the case of a toxic substance, the ED50 value can be used to determine the dose at which
a toxic effect is observed and can be used to establish safe exposure levels.
• The use of EC50 and ED50 values in subacute toxicity testing can also provide information
on the potency and efficacy of a substance over time.
• By measuring the EC50 or ED50 values at various time points during the subacute exposure
period, it is possible to assess changes in the potency and efficacy of the substance, as well
as to evaluate the potential for cumulative effects over time.
ADVANTAGES OF SUBACUTE TOXICITY STUDIES
Subacute toxicity studies are conducted to evaluate the toxicological effects of a substance
following repeated exposure over a period of weeks or months, typically up to 90 days. Some
advantages of conducting subacute toxicity studies include:
1. Mimics human exposure: Subacute toxicity studies typically involve repeated exposure
to a substance over a period of time, which better mimics human exposure patterns than
single-dose acute toxicity studies.
2. Detects delayed or cumulative effects: Repeated exposure to a substance over time can
reveal delayed or cumulative toxic effects that may not be evident in single-dose acute
toxicity studies. This can help to identify potential long-term health effects of a substance.
3. Provides dose-response information: Subacute toxicity studies can provide information
on the dose-response relationship for a substance, which can help to identify the no-
observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level
(LOAEL) for the substance.
4. Evaluates systemic toxicity: Subacute toxicity studies can help to evaluate the systemic
toxic effects of a substance, including its effects on various organs and tissues, as well as
on physiological functions such as metabolism, haematopoiesis, and immunology.
5. Assesses potential for accumulation: Repeated exposure to a substance over time can
help to assess its potential for accumulation in the body, which can be an important
consideration in evaluating the safety of a substance.
6. Supports hazard identification and risk assessment: Subacute toxicity studies can
provide important data that can be used to support hazard identification and risk
assessment, which are key steps in the process of evaluating the safety of a substance.

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SRINIVAS COLLEGE OF PHARMACY 9
DISADVANTAGES OF SUBACUTE TOXICITY STUDIES
While subacute toxicity studies have several advantages in evaluating the toxicological effects
of a substance following repeated exposure over a period of weeks or months, there are also
some potential disadvantages to consider:
1. Time and resource intensive: Subacute toxicity studies are typically longer and more
resource-intensive than acute toxicity studies, which can make them more expensive and
time-consuming to conduct.
2. Limited duration of exposure: While subacute toxicity studies involve repeated exposure
over a period of weeks or months, the duration of exposure is still limited compared to the
lifetime of an individual, which may limit the ability to fully evaluate the long-term health
effects of a substance.
3. Limited relevance to human exposure: While subacute toxicity studies can provide
important information on the potential health effects of a substance following repeated
exposure, the exposure levels and routes of administration used in animal studies may not
always be directly relevant to human exposure.
4. Limited evaluation of other factors: Subacute toxicity studies typically focus on the toxic
effects of a substance following repeated exposure, but may not fully evaluate other factors
that could affect the toxicity of the substance, such as interactions with other substances or
environmental factors.
5. Limited evaluation of rare effects: Subacute toxicity studies may not always capture rare
or idiosyncratic toxic effects that may only occur in a small percentage of individuals or
after long-term exposure.
CHRONIC TOXICITY STUDIES:
• Chronic toxicity refers to the adverse effects of a substance that occur after long-term or
repeated exposure, typically for a duration of months or years.
• Unlike acute and subacute toxicity studies, which evaluate the effects of short-term or
repeated exposure over a period of weeks or months, chronic toxicity studies aim to
evaluate the potential for a substance to cause long-term health effects.
• Chronic toxicity studies can be conducted in animals or humans, and may involve exposing
the test subjects to a substance at various doses over a period of months or years, depending
on the specific study design.
• The primary goal of these studies is to identify the long-term toxic effects of a substance,
including its effects on various organs and tissues, as well as on physiological functions
such as metabolism, haematopoiesis, and immunology.
• Some common health effects associated with chronic toxicity include organ damage,
cancer, and developmental abnormalities.
• Depending on the substance being studied, chronic exposure may also increase the risk of
other health problems, such as respiratory disease, neurological disorders, or cardiovascular
disease.
• Chronic toxicity studies are typically more complex and resource-intensive than acute or
subacute toxicity studies, due to the longer duration of exposure and the need to monitor
the test subjects over a longer period of time.
• In addition, interpreting the results of chronic toxicity studies can be challenging, as the
long-term effects of a substance may be influenced by many factors, including individual
differences in susceptibility, interactions with other substances, and environmental factors.

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• Despite these challenges, chronic toxicity studies play an important role in evaluating the
safety of substances over the long term, and are a critical component of the regulatory
process for assessing the potential health effects of chemicals, pharmaceuticals, and other
products.
• By identifying the long-term toxic effects of a substance, chronic toxicity studies help to
inform risk assessments and support decisions regarding the safe use and regulation of these
substances.
SIGNIFICANCE OF EC50 AND ED50 IN CHRONIC TOXCOLOGICAL STUDIES:
• The EC50 and ED50 values are important tools in chronic toxicity studies, as they help to
quantify the dose-response relationship between a substance and its toxic effects over the
long term.
• In chronic toxicity studies, the EC50 (effective concentration 50) represents the
concentration of a substance that produces a specific biological response or effect in 50%
of the test subjects over a prolonged period of time.
• Similarly, the ED50 (effective dose 50) represents the dose of a substance that produces a
specific biological response or effect in 50% of the test subjects over a prolonged period of
time.
• By measuring the EC50 and ED50 values, researchers can evaluate the potency of a
substance and its potential to cause toxic effects over a long period of time.
• In addition, the dose-response curve generated by these values can help to identify the
threshold of exposure beyond which the toxic effects become more severe, as well as the
range of exposure where the effects are most pronounced.
• The EC50 and ED50 values are also useful in evaluating the potential health risks
associated with chronic exposure to a substance, as they can provide information on the
dose levels at which toxic effects may occur.
• By comparing the EC50 and ED50 values to estimated or actual exposure levels in humans,
researchers can assess the potential for adverse health effects and inform decisions
regarding the safe use and regulation of the substance.
ADVANTAGES OF CHRONIC TOXICITY STUDIES:
Chronic toxicity studies have several advantages over acute and subacute toxicity studies,
including:
1. Long-term effects: Chronic toxicity studies evaluate the potential for a substance to cause
long-term health effects, which are often not observed in short-term studies. This helps to
provide a more comprehensive assessment of the safety of a substance.
2. Realistic exposure scenarios: Chronic toxicity studies typically involve exposure to a
substance over a prolonged period of time, which more closely mimics real-world exposure
scenarios than short-term studies.
3. Identification of delayed effects: Some substances may have a delayed onset of toxicity,
with effects appearing only after prolonged or repeated exposure. Chronic toxicity studies
can help to identify such delayed effects, which may be missed in short-term studies.

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4. Quantitative assessment: Chronic toxicity studies generate data that can be used to
determine the dose-response relationship between a substance and its toxic effects over
time, allowing for a more accurate quantitative assessment of the safety of a substance.
5. Regulatory requirements: Chronic toxicity studies are often required by regulatory agencies
to evaluate the safety of chemicals, drugs, and other substances, making them an essential
component of the safety evaluation process.
DISADVANTAGES OF CHRONIC TOXICITY STUDIES:
Chronic toxicity studies also have several disadvantages, including:
1. Time and cost: Chronic toxicity studies are typically longer and more expensive than short-
term studies, as they require prolonged exposure of test subjects to a substance. This can
make them difficult to conduct and may limit the number of substances that can be
evaluated.
2. Ethical concerns: Chronic toxicity studies involve exposing animals to potentially harmful
substances for prolonged periods of time, which raises ethical concerns about the use of
animals in scientific research.
3. Relevance to humans: There is often debate about the relevance of chronic toxicity studies
conducted in animals to humans, as there can be differences in susceptibility to toxicity
between species. This can make it difficult to extrapolate results from animal studies to
humans.
4. Limited endpoints: Chronic toxicity studies typically focus on a limited number of
endpoints, such as mortality or tumor incidence, which may not capture the full range of
potential health effects associated with exposure to a substance.
5. Interpretation of results: The interpretation of chronic toxicity studies can be complex, as
they often involve multiple endpoints and factors that can affect the results. This can make
it difficult to draw clear conclusions about the safety of a substance.
What is toxicity?
Toxicity refers to the ability of a substance to cause harm or adverse effects to living organisms.
What is poison?
Poison is a substance that, when ingested, inhaled, or otherwise absorbed into the body, can
cause harm or death. Poison can be natural, such as the toxins found in some plants and animals,
or synthetic, such as chemicals used in industry or household products.

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CLASSIFICATION OF TOXICITY BASED ON THE SPECIFIC EFFECTS:
There are many different types of toxicity that can be classified based on the specific effects
they have on living organisms. Here are some common types of toxicity:
1. Genotoxicity: This type of toxicity refers to the ability of a substance to damage DNA or
cause mutations, which can lead to cancer and other diseases.
2. Mutagenicity: This type of toxicity specifically refers to the ability of a substance to cause
changes in the genetic material of a cell, which can lead to mutations and cancer.
3. Carcinogenicity: This type of toxicity refers to the ability of a substance to cause cancer,
either by damaging DNA or through other mechanisms.
4. Teratogenicity: This type of toxicity refers to the ability of a substance to cause birth
defects or developmental abnormalities in a developing embryo or foetus.
5. Neurotoxicity: This type of toxicity refers to the ability of a substance to damage the
nervous system, leading to cognitive and behavioural changes, seizures, and other
neurological symptoms.
6. Hepatotoxicity: This type of toxicity refers to the ability of a substance to damage the
liver, leading to liver dysfunction and disease.
7. Nephrotoxicity: This type of toxicity refers to the ability of a substance to damage the
kidneys, leading to kidney dysfunction and disease.
8. Immunotoxicity: This type of toxicity refers to the ability of a substance to suppress or
stimulate the immune system, leading to increased susceptibility to infections or
autoimmune diseases.
9. Endocrine disruption: This type of toxicity refers to the ability of a substance to interfere
with the normal functioning of the endocrine system, leading to hormonal imbalances and
other effects.
10. Allergenicity: This type of toxicity refers to the ability of a substance to trigger an allergic
reaction in some individuals.