Landrigan Flashcards
Pharmacokinetic models
Physiologically based pharmacokinetic models that could describe unique features of young developing humans
Bioassay protocols
To provide direct information on the relative contribution of exposures at different ages to lifetime risks
Appropriate toxicological tests for perinatal and childhood toxicity
Two characteristics (other than consumption/breathing) that magnify children’s exposures
Hand to mouth behaviour
Play close to ground
Children’s metabolic pathways
Immature
Ability to metabolize, detoxify, and excrete environmental agents is different from adults
More or less vulnerable depending on the chemical
Children’s developmental processes
Easily disrupted during rapid growth and development before and after birth
Destruction of cells by chemicals, or endocrine mimickers influencing signalling
Children’s more years to live
More years to live, therefore more time to develop diseases initiated by early exposure
Thalidomide
Causes limb reduction defects following use in pregnancy
Aminopterin
Antagonist of folic acid
Associated with anencephaly, meningocele, hydrocephalus and cleft lip
Diphenylhydantoin
Broad spectrum of anomalies
Orofacial clefts, nail and digital hypoplasia, growth abnormalities, and mental deficiency
Valproic acid
Neural tube defects
Heart, craniofacial and limb anomalies
Coumadin
Hypoplasia of nasal cartialge, chondrodysplasias, atrophy of optic nerves
Endocrine disruption
Chemicals that have capacity to interfere with body’s hormonal signalling
Embryo, fetus and neonate, and child in prepubertal period are at high risk of adverse consequences
Child protective approach to risk assessment must include: (5)
1) Improved exposure assessment
2) Enhanced toxicity testing
3) New toxicodynamic and toxicokinetic models
4) Mechanistically based approach to hazard assessment
5) Application of uncertainty and safety factors that specifically consider children’s risks
