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DEVELOPMENTAL NEUROTOXICOLOGY (example of neurotoxicants (pesticide…
DEVELOPMENTAL NEUROTOXICOLOGY
Adverse effect
Morphological changes
Decrease in brain size/diameter (rukhsar)
reduce IQ
Leaning disability
GDP
impair executive function
Children (developing organisms) are more sensitive
The Blood Brain Barrier not fully develop
Placenta Barrier not fully develop cause so many chemical can pass through umbilical cord
Detoxification process incomplete
Development of the CNS occurs at different times/stages, different rate of development :
cell proliferation,....
Consequences of the effects(Rukhsar)
Antisocial behviour (rukhsar)
Criminal behaviour (rukhsar)
Violence(rukhsar)
Subtance abuse(rukhsar)
Slow down in economy(rukhsar)
Neurodegenerative disease(rukhsar)
Parkinsonism (Rukhsar)
Neurodevelopmental toxicants
Example of adverse effects- Silent damage
Consequences :
Alzheimer and Parkinson diseases, Loss of functions (Neurodegenerative diseases)
Definition of silent damage
: the deleterious effects are not clinically evident after exposure to the neurotoxicants : "persistent
biochemical or morphological injury which remains
clinically unapparent unless unmasked by experimental or
natural processes" Giordano and Costa, 2012
Barker hypothesis
: adult disease may have a fetal origin
Example of neurodevelopmental disorders
Cerebral Palsy (Rukhsar)
Autism(Rukhsar)
example of neurotoxicants
lead
dicrease of IQ (Iptissem)
methylmercury
Tragedy about methylmercury
manganese
Hyperactivity (rukhsar)
arsenic
Arsenic intoxication occur in which country?
fluoride
IQ decrement
solvents
risks for hyperactivity
aggressive behavior
pesticide
DDT
DDE
persistent and remain
organophosphate
eliminate rapidly
slow brain growth
thinning of the cerebral
toluene
maternal consumption of alcohol
Guidelines
Standard toxicity testing
Need to develop alternatives to conventional animal testing
Respect the law : REACH (Registration Evaluation
and Authorization of Chemicals) & Cosmetics Directive
Battery of tests needed for a precise evaluation of the toxicity
DNT (Developmental Neurotoxicity)
From gestational day 6 to post natal day 10 or 21 (and in the maternal milk)
PROBLEM :cry: : Overly sensitive & high rates of false positives (or the opposite way)
Use of mammalian cells in vitro or non mammalian model systems (useful for screening purposes)
OECD guideline?
Problems in DNT
ethics problems
no research on fetus (Iptissem)
not a lot of knowledge (Charlotte)
treatments maladjusted (Charlotte)
confuse autism and neurotoxicological diseases (Iptissem)
NEWLY RECOGNIZED NEURODEVELOPMENTAL NEUROTOXICANTS(Teha)
Manganese that can be found in drinking water can diminished intellectual function
A study stated that fluoride that found in water in China that exposed to children can decrease the IQ level
The exposure of mother to the chemicals in the workplace showed the tendency towards deficient neurological function.
NEW METHODS IDENTIFICATION OF DN( TEHA)
Tox 21 Program to promote evolution of toxicity
In-vitro method(rukhsar)
Neural stem cell (rukhsar)
Proposed Coordinated International Strategy (rukhsar)
Follow governmental regulation and market invention
(rukhsar)
Legally mandated testing of existing industrial chemicals and pesticides (rukhsar)
Legally mandated premarket evaluation of new chemicals before entering markets (rukhsar)
Formation of new clearinghouse for neurotoxicity (rukhsar)
Source to Neurotoxicant related disease(rukhsar)
Environment exposure(rukhsar)
Pesticides(Rukhsar)
Herbicides(rukhsar)
Smoking(rukhsar)
Lead in petroleum (rukhsar)
Air pollution(rukhsar)
Genetics(rukhsar)
Chemicals exposure at workplace(rukhsar)
Nurse(R)
Hospital employee(R)
Chemist(R)
Cleaner(R)
Hairdresser(R)
Beautician(R)
