Invivo Carcinogenecity Studies

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 1
INVIVO CARCINOGENECITY STUDIES
(Test guidelines : 451)
A Seminar as a part of curricular requirement
for I year M. Pharm II semester
Presented by
Ms. B. Mary Vishali
(Reg. No. 20L81S0104)
Department of Pharmacology
Under the guidance/Mentorship of
Dr. K. Somasekar., Ph.D.
Head of department of Pharmacology.

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• Introduction
• Principle of the test
• Description of method
• Procedure
• References
CONTENTS:

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• The original Test Guidelines 451 on Carcinogenicity was adopted in
1981.
• The updating of TG 451 has been carried out in parallel with
revisions of TG 452, Chronic Toxicity Studies, and 453, Combined
Chronic Toxicity/Carcinogenicity Studies.
• This TG is designed to be used in the testing of a broad range of
chemicals, including pesticides and industrial chemicals.
• Most of these studies are carried out in rodents so these TG are
designed primarily in those prospects.
• For non-rodent species, the principles and procedures are outlined in
this Guideline together with those outlined in OECD TG 409,
Repeated Dose 90-day Oral toxicity study.
INTRODUCTION:

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• The objectives of carcinogenicity studies covered by this test
guideline include:
-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;
- Characterization of the tumor dose-response relationship;

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
-Identification of a no-observed-adverse-effect level (NOAEL) or point
of departure for establishment of a Benchmark Dose (BMD);
-Extrapolation of carcinogenic effects to low dose human exposure
levels;
-Provision of data to test hypotheses regarding mode of action

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• The test chemical is administered daily in graduated doses to several
groups of test animals normally by oral route or by dermal or
inhalation route.
• The animals were observed closely for signs of toxicity and for the
development of neoplastic lesions.
• The animals may die during test process and are necropsied, and the
surviving animals were and necropsied.
Principle of the test:

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
1. Selection of animal species :- rodents (eg., rat and mice)
2. Housing and feeding :- animals may be housed individually or be
caged in small groups of same sex.
Temperature- 22⁰C( ± 3⁰C)
Relative humidity- 50-60%
Lighting- 12hrs light and 12hrs dark
Feed- diet as per guidelines and drinking water is supplied.
3. Preparation of animals :- healthy animals which are not involved in
previous experiments and which are acclimated for laboratory
conditions has to choose. The weight variation for each sex of animal
used should be minimal and not exceed ± 20% of the mean weight.
Description of method:

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• Number and sex of animals: each dose group and control group may
contain 50 animals of each sex.
• Provision for interim kills and satellite groups: during test study there
is a chance that animals may die due to development of
neoplasms(like 10 animals per sex), so to increase the statistical data
accuracy animals will be added (minimum of 5 animals per sex).
• Dose groups and Dosage: Atleast three dose levels and concurrent
control should be used. Dose levels should be choosen based on
shorter-term repeated dose study or range findings study. The data
related to toxicological and toxicokinetic information is taken into
consideration.
Procedure:

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• Preparation of doses and administration of test substances: usually
test substance is administered via oral route of administration, but
based of type of study route of administration will be varied.
• The test substance is dissolved in suitable vehicle and administer to
the test group in diet or drinking water or gavage while control group
is treated with only vehicle.
• For substances administered via diet or drinking water in long term
toxicity studies the concentration of chemical substance should not
exceed 5% of the total diet.
• In case of oral administration the test substance is given daily for
7days per week for a period of 24 months, and in case of dermal
administration test group is treated for 6hrs per day for a period of
24 months, and in inhalation route the test group is exposed for 6hrs
daily for a period of 24 months.

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• Duration of study: normally for rodents duration is 24 months for
some strains of mice 18 months will be sufficient(e.g., AKR/J, C3H/J,
C57BL/6J)
• Termination of study should be considered when the number of
survivors in the lower dose group or control group falls below 25%.
• In the case where only the higher dose group dies prematurely due
to toxicity, this should not trigger the termination of study.
• Survival of each sex should be counted separately.
• The study should not be extended beyond the point when the data
available from the study are no longer sufficient to enable a
statistically valid evaluation to be made.

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• Observations: all animals should be tested for mortality or morbidity,
toxicity, tumor growth and its location etc.,
• Body weight should be tested atleast once in a week for the first 13
weeks then once a month for next weeks.
• Food and water consumption should be measured once in a week
for the first 13 weeks and then once in a month for next weeks.
• Analysis of blood samples and urine samples has to be done.
• Gross necropsy has to be done for test and control groups for careful
observations of surface of body, all orifices , the cranial, thoracic and
abdominal cavities and their contents.
• Histopathology of all tissues from higher dose and control groups, all
tissues of animals dying or killed during study has to be done.

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• Data and reporting: all data regarding toxicity, onset of tumor
development, death or humane kill, signs of symptoms of all animals
should be included.
• Test report should include the following information:
Test chemical:
- physical nature, purity, and physicochemical properties;
- identification data;
-source of substance;
-batch number;
-certificate of chemical analysis;

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Vehicle (if appropriate):
-justification for choice of vehicle (if other than water);
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;
Test conditions:
- rationale for route of administration and dose selection;

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
- when applicable, the statistical methods used to analyze the data;
details of test chemical formulation/diet preparation.
- analytical data on achieved concentration, stability and homogeneity
of the preparation;
- route of administration and details of the administration of the test
chemical;
- for inhalation studies, whether nose only or whole body;
- actual doses (mg/kg body weight/day), and conversion factor from
diet/drinking water test chemical concentration (mg/kg or ppm) to the
actual dose, if applicable;
- details of food and water quality;

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
1. OECD (1995), Report of the Consultation Meeting on Sub-chronic
and Chronic Toxicity/Carcinogenicity Testing (Rome, 1995),
internal working document, Environment Directorate, OECD,
Paris.
2. EPA (2005). Guidelines for Carcinogen Risk Assessment Forum
U.S. Environmental Protection Agency Washington, DC.
3. OECD(2009),Draft Guidance Document on the Design and
Conduct of Chronic Toxicity and Carcinogenicity Studies, Series on
Testing and Assessment No. 116.
REFERENCES :

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR

Invivo Carcinogenecity Studies

Recomendados

Recomendados

Mais conteúdo relacionado

Mais procurados

Mais procurados (20)

Semelhante a Invivo Carcinogenecity Studies

Semelhante a Invivo Carcinogenecity Studies (20)

Mais de Raghavendra institute of pharmaceutical education and research .

Mais de Raghavendra institute of pharmaceutical education and research . (20)

Último

Último (20)

Invivo Carcinogenecity Studies