Exam 2 Flashcards
US Prohibition
1919-1933, Dr. Chales Norris and Alexander Gettler warned of danger of wood alcohol, causing death and blindness
Methanol
Breaks down into formaldehyde and formic acid in the body as it’s metabolized, formic acid causes delamination of the optic nerve (loss of myelin sheath around nerve fiber)
Ethanol
exhibits hormesis, tetatogen (fetal alcohol syndrome) alcohol diffuses through the placenta (conc of fetus blood same as mothers in a few min) metabolizes alcohol faster and stays in fetus longer, causes physical, behavioral and cognitive impairments
Traits of fetal alcohol syndrome
loss of philtrum (vertical groove between base of nose and border of the upper lip), epicanthal folds (a skin fold of the upper eyelid covering the inner corner of the eye)
Multiple effects of medicines
desired-therapy
undesired-side effects
ex) coumadin (warfarin) is blood thinner that helps with BP but causes bleeding from everywhere
ex) diphenhydramine (Benadryl) is antihistamine but causes drowsiness
Allergic reactions
small molecules (haptens) are mostly unnoticed by the immune system, they may eventually combine with a protein to form an antigen which triggers antibiodies
after expose to this happen and antigen-antibody interaction happens (this causes allergic response)
delayed toxic effects
occur after some period of time
immediate toxic effects
occur or develop rapidly after single exposure
Carcinogenic
effects of chemicals can have long latency periods
latency period=time of cancer initiation to time of cancer detection
Induction period influences
dose/intensity of exposure
duration of exposure
the type of substance
the type of cancer from exposure
age at exposure
gender
genetics
Latency
period between disease initiation and detection
induction
period between causal action and disease initiation
local vs systemic toxicity
local occur at site of immediate contact
systmeic require absorption and distribution of the molecule from its entry spot to another site at which the effect is produced
Reversible vs irreversible toxic effects
most injuries to liver are reversible because liver tissue regenerates efficiently. Most injures to the CNS are irreversible because the CNS does not regenerate well
Spectrum of undesired effects
1)allergic reactions
2)immediate vs delayed toxicity
3)reversible vs irreversible
4)local vs systemic
tolerance
reduced toxic response to a chemical because of prior exposure to that chemical or to a structurally similar chemical
Pharmacokinetics
study of what the body does to the drug or the study of the time course of drug absorption, distribution, metabolism, and excretion
Pharmacodynamics
study of what the drug does to the body or the relationship between drug concentration at the sit of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects
Bernardino ramazzini
published book on occupational disease linking diseases to hazardous chemical exposure
helped establish occupational medicine and occupational toxicology
established importance of prevention rather than cure (like green chemistry)
Percivall Pott
recognized role of soot in scrotal cancer
first report of polyaromatic hydrocarbon carcinogenicity
lead to improved medical practices and prevention
Source of polyaromatic hydrocarbons (PAH)
occur naturally in coal, crude oil, and gasoline
Naphthalene (moth balls) are simplest
also called polycyclic organic matter (POM)
produced by incomplete combustion or high pressure processes when burning coal, oil, gas, wood, garbage, and tobacco
formation of PAHs and MOA
many small organic molecules released during burning of fuel, through surface growth and coagulation for PAHs
epoxides covalently bind to N atoms on guanine with epoxide ring opening yielding both cis and trans adducts (disrupts DNA shape)
Moth balls
small balls of chemical pesticide, sometimes used when storing clothing and other material from silver fish or clothes moth larvae, used naphthalene (flammable) of 1,4-dichlorobenze (carcinogen) released gasses to kill insects
replaced with camphor
Claude Bernard
French physiologist who established use of scientific method in medicine, used blind experiments and established concept of homeostasis, experimented on rabbits
Friedrich Wilhelm Adam Serturner
german pharmacist and pioneer of alkaloid chemistry
discovered morphine
Morphine
biosynthesized in opium poppy, used as pain reliever, chronic use causes tolerance
Morphine affect on body
produces most of its analgesic (relieves pain) effects by binding to the mu-opioid receptor with the CNS and PNS
Morphine MOA
chronic expose to morphine causes phosphorylation of opioid receptors by GRKs
phosphorylation prepare opioid receptors for arrestin binding (arrestin are proteins that in active phosphorylated GPCRs and block interaction with G proteins) Arrestin binding blocks further G protien0mediated signaling inducing desensitization of opioid receptors
CNS
brain and spinal cord
PNS
everything else, nerves that travel from you spinal cord and brain to supply your face and rest of your body with signals
Autonomic
nervous system processes your brain runs automatically and without you thinking of them
somatic
functions you manage by thinking about them
Which material is more toxic to consume, methanol or ethanol? Explain
Methanol! It is slowly metabolized eventually interrupting the mitochondrial functions and demyelinates the optic nerve, leading to loss of vision and death. While EtOH is toxic, its oxidation products are less toxic (acetic acid) than methanol oxidation (formic acid) the “cure” for methanol poisoning is ethanol, indicating that health care professionals believe that ethanol is less toxic than methanol
A hapten is
a) also called an arrestin
b) part of CNS
c) small chemical grouping which reacts with preformed antibodies
d) the most sampled body fluid
e) part of PNS
C
Explain why the molecule chrysene (large aromatic) fits below into the class of molecules called polyaromatic hydrocarbons?
Chrysene has multiple aromatic rings and is solely composed of C’s and H’s (hydrocarbon)
What is the name of the time between completion of a component cause (exposure to toxic agent) and disease occurrence?
a) induction period
b) latency period
c) tolerance period
d) desensitization period
A
What is meant by the acronym PFAS?
PFAS molecules contain a lot of flourine. The P is for “per” meaning fluorine is in all possible carbon bonding positions but not all PFAs are completely fluorinated
Name two products that conatin PFAS molecules
stain resistant, water resistant, paints, firefighting foam
If a chemical changes gamete production it’s classified as a
a)aquatic toxin
b)reproductive toxin
c) developmental toxin
d) Covid vaccine
B
When did Rachel Carson publish silent spring
a) 1860s
b) 1920
c)1960s
d)1980s
e)2000
C
Why did paint companies use so much lead in their products (until banned)
Highly colored pigments, catalysts for drying, corrosion inhibitor
Paradox of uncertainty
Human testing needed for pharmacuticals but also can’t fully know risks until human tested. Many people don’t want animal testing and using cellular/computational models leads to controversy with results
Need to balance human safety and human trials
Morphine absorption
inhibits GABA inhibitors
significant amount of first pass metabolism, only 40-50% make it to nervous system
morphine processed in the kidneys and eliminated in urine
Mu vs kappa receptor
both on membrane of neuronal cells and both opioid receptors that can cause pain relief
Mu leads to euphoria, addition, respirator depression
kappa leads to dysphoria and sedation
Pure food and drug act
1906, Harvey Wiley, and Upton Sinclair, under law drug makers had to list ingrediants deemed dangerous and can’t mislabel ingrediants
law banned adulterated or mislabeled food and drug products and made food inspectors
Food and Drug Administration
1930 inspired by work of Harvey Wiley in the Pure food and Drug Act
Carcinogen
Any substance capable of causing cancer, cells showing both uncontrolled growth and a tendency to invade and destroy other tissues. Cancer typically manifests in a tumor that arises from normal tissue but serves no physiological function
Rachel Carson
Author of the book
Silent Spring (1962) that is widely credited to birth the
environmental movement. An author, marine
biologist and conservationist, Rachel wrote about the
effects of pesticide use on wildlife, causing public
concern. Her work led to the development of the EPA
and the banning of the synthetic pesticide DDT
Olga Huckins
friend of rachel carson, upset when birds died
Lead based paints
Banned in 1977
Why lead in paints?
Pigments
Usually: lead chromates, lead oxides, lead molybdates, lead sulfates,
Catalysts for cross-linking to speed drying (lead octoate, lead napthentate)
Inhibit corrosion (lead tetroxide)
lead compounds in paint
many oxophilic (oxygen loving), many use phosphate (PO4 3-)
BPA
Bisphenol A (2 aromatics together with OH on both) in plastics until 2012, particularly baby bottles and water bottles, endocrine disruptor
PFAs
perfluorinated chemicals, persistant,, industry moving to alkyl chain alternatives “have at least two adjecent carbon atoms, where one carbon is fully flourinated and the other is at least partially fluorinated
PFAs in products
firefighting foams, microwave popcorn bags, water resistant clothes, paint, stain resistants, cosmetics, peticides, photography, stain resistant furniture, non stick pans,
Endocrine system
7 glands and organs, using hormones to control and coordinate your body’s metabolism, energy level, reproduction, growth and development, and response to injury, stress, and mood
Endocrine disruptors
chemicals with Estrogen-like and anti-androgen effects causing damages to different tissues and organs, including reproductive system, immune system and neuroendocrine system, etc.
Estrogen
group of hormones that play an important role in the normal sexual and reproductive development in women.
Androgens
a group of sex hormones that give men their ‘male’ characteristics(such as testosterone)
How endocrine disrupting chemicals affect hormone activity in body
can increase or decrease normal hormone levels, can mimic the body’s normal hormone levels, can alter the body’s natural production of hormones
What is carbonate
carbon single bonded to two oxygens and double bonded to one oxygen
polycarbonate water bottles
bisphenol-A + Diphenyl Carbonate= Bisphenol-A Polycarbonate
Transesterification route
also releases phenol
not all BPA linked in production and leeches out
Alternative poly carbonate synthesis
mainly uses phosgene which can cause extreme lung damage
can also do BPA and phosgene synthesis
Paul Anastas
one of the originators of green chemistry
what are the 3 kinds of toxicants?
reproductive developmental and aquatic
Reproductive toxicants
chemicals that interfere with normal sexual function and fertility
What might a reproductive toxicant interfere with
Onset of puberty
Gamete production and transport
Reproductive cycles
Sexual behavior
Pregnancy outcomes
Sperm count or shape
Cadmium
Shows up same places as lead (pigments, ect). LEGOs and toys
deteriorates sperm motility and synthesis of hormones
impairs female reproduction and reproductive hormonal balance and menstrual cycles
What is DEHP (structure)
Bis (2-ethylhexyl)phthalate
aromatic with two chains of carboxilic acid and carbon chains
where is DEHP found
Added to plastics to make them flexible
Often in: tablecloths, floor tiles, furniture upholstery, shower curtains, garden hoses, swimming pool liners, rainwear, baby pants, dolls, some toys, shoes, automobile upholstery and tops, packaging film and sheets, sheathing for wire and cable, medical tubing, and blood storage bags.
What are the harms of DEHP
demonstrated to cause developmental toxicity, such as birth defects, in rats and mice from oral exposure. Reproductive effects, such as decreased fertility, proportion of pups born alive, and testicular weights and tubular atrophy, have also been noted from oral exposure to DEHP in animals.
Dr. Frances Kelsey
Prevented Thalidomide (a developmental toxicant) from being released on US markets, 1960s, awarded presidents award for work
Developmental toxicants
cause adverse effects on development of offspring, induced during pregnancy or as result of parental exposure
Some symptoms of developmental toxicants
Death of the developing organism
Structural abnormality
Altered growth
Functional deficiency
Manifest at any point in lifespan
Teratogens – substances that cause birth defects
examples of developmental toxicants
thalidomide mercury, retanoic acid
Thalidomide toxicity
Only S-(−)-thalidomide is teratogenic
Disrupts blood flow to developing limbs
Possibly useful for tumor inhibition
Undergoes racemization in the body
Modern uses for thalidomide
Anti-inflammatory
Leprosy
Used with dexamethasone for multiple myeloma
Why is thalidomide no a valid argument against covid vax?
Medications (like Thalidomide) are small molecules which can interact with cell receptors, causing a response
Small molecules can interact with many different cell receptors, triggering the “unintended consequences” (side effects)
vaccine is pieces of mRNA
Thalidomide undergoes racemization, mRNA vaccines do not
Vaccines have been used for many years, with mRNA vacciens studied since the 1970’s
Acute aquatic toxicity
is the intrinsic property of a substance to injure an aquatic organism after a short-term exposure.
Chronic aquatic toxicity
is the potential or actual properties of a substance to cause adverse effects to aquatic organisms during long-term exposures in relation to the life cycle of the organism.
WET
Whole effluent toxicity
the collective toxicity of all water flowing into a wastewater treatment plant
CuSO4 aquatic toxicity
Trout, koi and juvenile fish of several species are known to be particularly sensitive to copper.
Acute: Fish kills have been reported after copper sulfate applications for algae control (algicide) in ponds and lakes. (Caspian fish show LC50=2.3ppm and 10-20ppb is acutely toxic)
Chronic: Reproduction, growth, brain function issues
why is Cu needed for life
cytochrome c oxidase in the mitochondria, lysyl oxidase in connective tissue, dopamine monooxygenase in brain, and ceruloplasmin.
apical endpoint
what is observed as concentration increases
Chlormequat
aplied to oat and grain crops, alters a plants growth, preventing it from beinding over and makin it easier to harvest, in cherios ect.
may cause infertility and delayed puberty
3 main exposure pathways
inhalation (breathing into lungs)
absorption (soak through skin)
ingestion (swallowed)
Inhalation
Chemicals in the air can be breathed in through the nose or mouth.
Gases and vapors are absorbed through the lungs directly into the bloodstream.
Dusts, particulate matter and mists can settle into to different parts of the respiratory tract depending on the particle size.
How is size of particulate mater related to toxicity?
Coarse (bigger) particles, PM10
Can irritate your eyes, nose, and throat. Dust from roads, farms, dry riverbeds, construction sites, and mines are typical sources
Fine (smaller) particles, PM2.5
More dangerous
Can penetrate into deep parts of your lungs, possibly enter the bloodstream
exposure to PM
acute exposures lead to cardiovascular events, chronic exposure increase risk of strokes coronary heart disease and premature death
7 mil die yearly in lower income countries
Skin absorption
Some chemicals can pass through the skin into the body and cause health problems.
Some chemicals can affect the skin directly causing irritation or dermatitis.
Ingestion (swallowing)
Chemicals can rub off dirty hands and contaminate food or drink.
Chemicals in the air can settle on food or drink and be swallowed.
Chemicals that are swallowed can be absorbed in the digestive tract.
Development of EPA
1970, US environmental protection agency
Established by the Nixon administration, with the goal of creating a branch of government who would help to maintain clean air, land and water and regulate pollution in the environment.
Love canal foundation
William Love bought love canal for hydroelectric, left hole in land
hooker chemical dumped hazardous waste in hole and sealed with clay cap, school built over site (hooker clause meant hooker couldn’t be blamed for problems), homowners lived their from 1950s-1970s until Calspan Coorporation in late 70s alongside Newyork State Department of Health found there were dangerous chemical contamination
Love Canal solution
New york state department did little other than evacuate women and children, state then agreed to evacuate and buy houses by President Carter in 1980
Love canal summary
A chemical and plastics company had used an old canal bed as a chemical dump from 1930s to 1950s. The land was then used for a new school and housing track. The chemicals leaked through a clay cap that sealed the dump. It was contaminated with at least 82 chemicals (benzene, chlorinated hydrocarbons, dioxin).
Health effects of the people living there included: high birth defect incidence and seizure-inducing nervous disease among the children
What did love canal inspire?
the formation of Superfund, aka CERCLA
Superfund
After Love Canal and Valley of the Drums, Congress approved the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), “Superfund”!
It allows EPA to clean up sites and forces the responsible parties to clean the sites (makes the polluters clean their mess!)
PresidentJimmy Cartersigned theSuperfundbill into law on December 11, 1980. Part of theSuperfundpayment toLoveCanalincluded $20 million to moveLoveCanalresidents into saferneighborhoods.
NPL
national priorities list, the most harmful locations on the superfund list
Valley of the drums solution
Uncontrolled industrial waste dump in Kentucky
EPA installed clay cap, perimeter drainage system, groundwater monitoring wells and security fence to help with contamination (started 1987, off NPL by 1996)
Valley of the Drums Cause
23 acres, near Louisville KY
Many chemicals were dumped with heavy metals and polychlorinated biphenyls (PCBs)
This was the “nightmare”
Caught fire and burned for a time in 1966, owner died in 1977, no law gov’t to step in & clean…
Along with Love Canal, an inspiration for Comprehensive Environmental Response, Compensation and Liability Act
Persistant Organic Pollutant (POP)
Chemicals that take a long time to break down once released to the environment
DDT and PCBs
both heavily halogenated (chlorines)
DDT=dichlorodiphenyltrichloroethane PCB = polychlorinated biphenyl
PCBs are part of a new classification: Dioxins
TCDD and PCDF (polychlorinated dibenzofurans)
Times Beach
1982-1985): A small town in Missouri in 1982 the soils along the roads were contaminated with dioxin (from contaminated waste oil). The levels of dioxin (TCDD) were at 300 to 740 ppb. A flood in late 1982 forced ~700 families to leave their homes. The federal government bought the town using $33 million for toxic waste clean-up. By 1985 all the residents were out of the town and it was dis-incorporated.
Times Beach was a Superfund site until 1999 when the site opened as a state park to commemorate route U.S. 66 and the history of the Times Beach area
Theo Colborn
1988, scinetist of mammals and effects of man-made chemicals on offspring, creates “Wingspread statement” which is where the term endocrine disruption was coined
writes “Our Stolen Future” which is about ambient exposure effects of endocrine disruptors
What determines too much chemical exposure
called “permissible exposure limits - PELs” or “threshold limit values - TLVs”
Workplace limits or allowable amounts in the air that people can be exposed to without known harmful effects.
Hierarchy of Controls
Best -> worst
elimination, substitution, engineering controls, administrative controls, PPE
Thomas Midgley
TM was the man whose research suggested TEL would “fortify” gasoline,
reducing knock
Initially, he was NOT in favor of TEL, he had championed ethanol just prior
to TEL due to the adverse health effects. NOTE: It was impressive that he washed
his hands in TEL to show its safety. But I wonder if it was a showmanship trick, and
he did NOT wash in TEL (already knowing of its dangers!)
Robert Kehoe
Medical consultant to Ethyl and toxicologist who studied lead
levels in humans. Erroneously concluded lead levels in modern humans were not
elevated due to incorrect control group
