Gen Tox Exam 2

Specialized toxicology

hormones system

feedback process, very sensitive, similar to both

testosterone regulation

hypothalamic-pituitary-gondal feedback system

Estrogen regulation

hypothalamic-pituitary-gondal feedback system: LH and FSH promote synthesis of estrogens and progestins

ovary protection

no protection, no specialized barriers

thalidomide importance

the substance that changed everything

thalidomide disaster history

West German experience of 1960 - large newborns with limb malformations, CHD, organ abnormalities

thalidomide introduction

1956- as a sedative/hypnotic and nausea/vomiting for pregnancy

thalidomide testing

prenatal toxicity in at least 19 species

period of heightened susceptibility

organogenesis

4 major effects of prenatal exposure

embryo lethality, malformations, growth slowing, structural defects/functional deficits

government regulation

seeks to affect human behavior and settle disputes

regulators act when

before knowledge is complete

symbiotic agencies

regulatory agencies can dictate types of testing

how regulators look at things

cancer vs all other effects

FDA regulates

starting 1906, food, drug, and cosmetics for any added poisonous or deleterious substance

Risk assessment

systematic scientific evaluation of potential adverse health effects resulting from human exposures to hazardous agents or situations

Three types of epidemiological studies

cross sectional, cohort, case controlled

cross sectional studies

surveys groups of humans to identify risk factors and disease, not useful for establishing cause and effect, qualitative

cross sectional example

if there are more smokers that have lung cancer than nonsmokers

cohort studies

evaluate individuals based on known exposure, monitor for disease development, establish rate after exposure, quantitative

cohort example

smokers and non smokers over time to estimate cancer

case controlled studies

individual chosen based on disease vs non disease status, exposure history used to establish common features, always retrospective, most important

case controlled example

demonstration of link between smoking and lung cancer, proved by cohort later

dose-response approach to risk assessment

threshold- dose below which no biological response occurs

threshold appraoches

NOAEL, LOAEL

NOAEL

highest non statistically significant dose tested, not risk free

LOAEL

lowest dose tested with a statistically significant effect

nanotechnology

development and application of material and structures with nanoscale dimensions (1-100nm)

carbon based nanomaterials

fullerene, carbon nanotubes (CNTs), related products

nantoxicology main characterization

size, surface area (smaller= greater surface area)

standard toxicity testing limits

nanomaterials may interfere with common assays due to large surface area, absorb proteins

mechanism of toxicity of nanomaterials

oxidative stress- generation of reactive oxygen series (ROS)

single use and short lived plastics effect

account for 40% production, increasing every year

why plastic production increasing rapidly

fossil carbon industry pivoting away from producing fuels and redirecting their investment into plastics and petrochemicals

harmful chemicals in plastics

16000+ chemicals are responsible for plastics’ known harm to health, carcinogens, development neurotoxicants, endocrine disruptors

womb and young children plastic vulnerability

exposure prevention is the only effective treatment

cardiovascular hazards of microplastics

patients with MNPs have 4.5 fold (450%) increase in risk for nonfatal myocardial infarction, nonfatal stroke, or death over next 3 years

MNPs

microplastics and nanoplastics (MNPs)

tips for microplastic free lab

replace plastic with glass or steel, use plastic free water filtration system, wear 100% cotton lab coats, use spray bottle or air filters to reduce dust, allow cleaners in designated areas only, no hairspray or cosmetics that flake, fewer people in lab to prevent airborne circulation

acute coma treatment

DONT: dextrose, oxygen, naloxone, thiamine

acute coma assessment

TONGS: toxin/trauma, oxygen, nonconvulsive status epilepticus, glucose, stroke/sepsis

toxic syndrome

cholinergic - muscarinic, nicotinic

muscarinic symptoms

DUMBBELS, CNS and periphery

nicotinic symptoms

fasiculation, weakness, paralysis /blockade, autonomic ganglia

medical diagnostic technique

anion gap serum

anion gap

difference between unmeasured anions (prot, organic acid, phosphate, sulfate) and measured cations (K+, Ca++, Mg++)

toxin effect on anion gap

increase AG due to accumulation of organic acids

gut decontamination

activated charcoal- large surface area, traps toxins with MW 100-1000amu

cathartics

saccharides- sorbitol

forensic toxicological approach to cases

history (always start), gross body or autopsy observations, microscopic autoopsy findings, specimens, analyses

preferred specimen for forensic

heart blood

screening analysis ex

GC-MS

ethyl alcohol forensic effect

more commonly contributory than a direct cause of death, can be fatal

carbon monoxide senses

no smell, no color, no taste

criteria to be chemical warfare agent

ease of large scale production, ease of storage, ease of dispersal, ease of action, incapacitation, auto-protection

mustard agent characteristics

sulfur and nitrogen, lipid soluble, incapacitating

mustard agent MOA

alkylating agent, cross link guanine, cholinomimetic

benefit of lewisite

creation of BAL (british anti lewisite)/dimercaprol

increase toxicity of nerve agents

increase absorption during exercise

latency period of phosgene

30min to 24hr

food allergy

immune mediated response

food anaphylaxis

immune mediated, more severe than allergy

food anaphylaxis example

sulfite sensitivity - preserved foods and wines

food intolerance

reactions that are not readily explained

food intolernce example

celiac disease- wheat, rye, barley, oats

food poisoning

effect caused by direct action of food or food additive, may be from microorganisms or parasites

food idiosyncrasy

genetically determined hypersensitivity

food idiosyncrasy example

lactose intolerance

pharmacological food reaction

adverse reaction to food, natural additive, or added chemicals that produce drug like effect

pharmacological food reaction example

cheese- tyramine, severe headache or hypertension, deadly in MAO inhibitors

metabolic food reaction

toxic reactions to food when eaten in excess or improperly prepared

metabolic food reaction example

lima beans- cyanosis

venomous

animals that can produce poison in secretory glands or cells and deliver in bite or sting

poisonous

animals whose tissues, in part or whole, are toxic; occurs via ingestion

major danger of getting antivenom/antivenin

anaphylaxis reaction

venom composition effect on connect tissue

hyaluronidase- hydrolyze tissue with hyaluronic acid

bites can occur

after snake is dead or decapitated via reflexes

some envenomation requirement

prolonged contact

batrachotoxin target organs

nuerotoxic, cardiotoxic

hymenoptera (bees, wasps, ants)

group accounts for more death each year in US than all other venomous creatures

not venomous american spiders

only 2 of 20,000

jellyfish effect

cause histamine release

stingray attack

can kill