seminar on teratogenicity by sumaraja
Post on 15-Jan-2015
2.941 Views
Preview:
DESCRIPTION
TRANSCRIPT
WELCOME
WELCOME
UNDER THE GUIDENCE OF BYMISS MEENU SINGH SUMANGALI.MASST. PROFESSOR M.PHARM DEPARTMENT OF PHARMACOLOGY PHARMACOLOGYCMRCP HYDERABAD
TESTS FOR TERATOGENICITY
Teratogenicity:
The capability of producing fetal malformation
A teratogen is an agent that can produce a permanent alteration of structure or function in an organism exposed during embyronic or fetal life
Teratogen:
A given teratogen may be organ specific.
It may be species specific. It can be dose specific.
Basic Characteristics of teratogen:
Teratology:
Teratology is the study of abnormalities of physiological development.
It is often thought of as the study of human “birth defects”, but it is much broader than that, taking in other non-birth developmental stages, including “puberty “; and other non-human life forms, including plants.
Critical periods:
STAGE OF EXPOSURE
OUTCOME(S)
Pre-implantation Embryonic lethality
Implantation to time of organogenesis
Morphological defects
Fetal → neonatal stage Functional disorders, growth retardation, carcinogenesis
Historical Teratogens:
Thalidomide
Accutane
Diethylstilbestrol(DES)
Alcohol
CLEFT LIP
PHOCOMELIA
AMELIA / PHOCOMELIA
TESTS FOR
TERATOGENICITY
Testing Protocols:
Under the guidelines of FDA Under the guidelines of ICH
Tests under FDA:
Multigenerational studies
Single generational studiesa) Segment I:Evaluation of Fertility
and Reproductive Performanceb) Segment II: Assessment of
Developmental Toxicityc) Segment II: Postnatal
Evaluation
Tests under ICH:
Fertility Assessment
Postnatal Evaluation and Pregnancy State Susceptibility
Assessment of Developmental Toxicity
Multigenerational Study:
The animals are mated.
Continuous exposure of a rodent species (usually mice)
F1
Exposed shortly after weaning (30–40 days of age)
The effects of the test is monitored through each generation.
The measured parameters : Fertility Litter size Neonatal viability
F2F3
Evaluation of Fertility and Reproductive Performance:
Male rodents are treated for 70 days and nonpregnantfemales for 14 days .Treatment is continued in the females during Mating Pregnancy Lactation
50% of the females are killed and the fetuses are examined for presence of malformations. The other 50% areallowed to give birth. After weaning, these offspring are killed and necropsied
Assessment of Developmental Toxicity:
Treatment of pregnant females only during implantation through organogenesis
One day prior to birth, the animals are killed
Fetuses examined for 1.viability 2.Bodyweight 3. presence of malformation
Postnatal Evaluation:
Pregnant animals are treated from the last trimester of pregnancy until weaning.
Evaluation: Parturition process Late fetal development Neonatal survival Growth Presence of any
malformations
Fertility Assessment:
1. 3.
Males Females
Exposed for four weeks before mating
Two weeks before mating
Evaluation Evaluation
Reproductive organs weight Fertility
Histological analysis Litter size
Sperm count & mobility Viability of conceptus
Postnatal Evaluation and Pregnancy State Susceptibility:
Comparing the degree of toxicity of the non pregnant female to that of the pregnant female
Evaluation : Maternal toxicity Growth Functional
development(off springs)
Assessment of Developmental Toxicity: Pregnant animals are exposed from implantation through organogenesis
The study is conducted using atleast two species, one rodent and one non rodent.
One day prior to birth , the animals are killed & fetuses are examined.
Evaluation : Viability Body weight Presence of malformation
Alternative Test Methods:
Micro mass test ( cells from the limb buds & brains of rat embroys)
Whole embrio culture test(whole embryos of rats)
Embryonic stem cell test
Conclusions: Understanding the mechanisms of the
induction of birth defects is key to determine how to prevent these effects.
Further increasing the accuracy of experimental animal extrapolation will aid in the interpretation of experimental data in order to more accurately determine the risk of a given compound to elicit birth defects in humans
Please, give only good fertilizer…
top related