Toxicity Lecture 2

The Case of Jennifer Strange YES or NO Is there a substance that is toxic at any dose? YES or NO Is there a substance that is safe at any dose? america/radios-deadly-stunts-the-jennifer- strange-story

Environment Everywhere we live, work, learn, play…

Our Environment Is Everything We Come in Contact With Through EatingIngestion DrinkingIngestion BreathingInhalation TouchingDermal Absorption Routes of Exposure

Bell-shaped Curve Not everyone reacts the same way Different folks different susceptibilities “Average” Susceptibility Very Great Susceptibility Very Low Susceptibility Genes Nutrition Health Status Stress Other

Safe Unsafe

Our Understanding is a lot like Swiss Cheese We don’t even know what we don’t know yet. Our tools are not as good as they need to be.

So much that we don’t know About 80,000 chemicals in commercial use Only about 550 in EPA’s risk database, with toxicity information Some toxicity information available for pesticides The gaps in our knowledge seem to be bigger than our actual knowledge

Dose / Response How Chemicals Act in the Body Usually think of cancer causing chemicals as having no threshold

Toxicity is dependent upon: Dosage Amount Number of times organism is exposed Size and Age of Organism (Life Stage) Synergistic Toxicity Ability of the organism’s body to detoxify Organism’s Individual sensitivity to that substance.

Dosage Dose contribution to toxicity we have discussed in great detail – Scenario’s – Liver Cell Lab – Dose-Response Curve Activity

Size and Age of the Organism-Life stages Which life stage do you think creates the greatest vulnerability?

Children Are Not Little Adults Children’s Increased Vulnerability Windows of Vulnerability in Development

Adult’s “Machinery” is OFF

Children’s “Machinery” is ON

Children Are Not Little Adults Children’s Increased Vulnerability Windows of Vulnerability in Development Differences in Physiology

Exposure Differences : Physiology Pound for pound, kids – breathe more air than adults – drink more water than adults – eat more food than adults – have increased surface area to body mass ratio relative to adults May also have different metabolism routes, speeds due to enzyme availability or activity

How many twelve ounce drinks/day would an adult male need to consume in order to take in proportionately as much as an infant? Infants Adults 35

Number of times an organism is exposed Behaviors that lead to exposure Environment available to the organism Life span of the organism The following slides provide examples specific to children

Children Are Not Little Adults Children’s Increased Vulnerability Windows of Vulnerability in Development Differences in Behaviors Differences in Physiology

Exposure Differences : Behaviors Closer to the ground Diet and eating habits differ – Newborns - breast milk or formula – Infants / Toddlers - more fruit and milk products – “Fussy Eaters” abound – “Grazing” is common

Exposure Differences : Behaviors Engage in more potentially high-risk behavior – increased hand contact with “stuff” – increased mouthing behaviors – more time spent outdoors

Average child eats X times more apples than an adult, not accounting for child’s smaller size. X= _______ Adults Non-nursing Infants 6.9 times

Synergistic Toxicity Synergistic Effect- two or more harmless chemicals become toxic when mixed together Synergistic Toxicity- Two or more harmless chemicals accumulate in an organism and become toxic when combined

Final Toxicity Consideration Organism’s ability to detoxify Genetic Overall health of the individual Organism’s ability to get away from the toxin while detoxifying Individual Organism’s Sensitivity Genetics Allergies Timing of the exposure Synergistic toxicity

Exposures Acute Toxicity Immediate, short term effects of exposure to toxins Example – Food Poisoning Chronic Toxicity A Physiological effect is not immediately apparent for months or years after exposure Also- the low dose of a toxin over a long period of time Example-Dry Cleaning Chemical in drinking water

Accumulations Bioaccumulation- toxins build up in an organism over time Biomagnification- toxins are passed through a food chain