Study Guide Material Flashcards
Dx criteria for multiple chemical sensitivity? (6)
- sxs are reproducible w/repeated chemical exposures
- condition has persisted for significant period of time
- low levels of exposure results in manifestations of the syndrome
- sxs improve when the triggering chemicals are removed
- responses often occur to multiple chemically unrelated substances
- sxs involve multiple organ systems
what is sick building syndrome? ssxs? potential contributing factors?
sxs of ill health that seem to be linked to a building but no specific cause is identified
ssxs: fatigue, H/A, nausea, EENT irritation, chest tightness, asthma, poor concetration, memory loss
potential contributing factors: chemicals, mold, recirculation of air, poor ventilation
what is building related illness?
recognized diseases caused by being in a building
what is the main chemical in a Brazilian Blow-out?
formaldehyde
what is the maternal occupation with increased risk of cleft palate in their children?
preschool teacher
what is natural gas formed by? composition of natural gas?
formed when layers of buried plant and animal material is exposed to intense heat and pressure over thousands of years
composition: hydrocarbon gas mixture consisting mostly of methane and to a lesser degree carbon dioxide, nitrogen and hydrogen sulfide
health effects of exposure to hydrogen sulfide component of natural gas?
higher RBCs, Hct, Hgb, platelets, lower WBCs
respiratory sxs in ppl who used gas appliances
what can you potentially be exposed to if a compact fluorescent bulb breaks?
small amounts of mercury
what is the toxic component in teflon cookware?
polytetrafluoroethylene or PTFE
what is the proven method to accelerate clearance of PFCs (perfluorinated compounds)?
no proven method!
what are the bioaccumulation concerns of PTFE and PFCs?
reproductive, toxicity, neurotoxicity, hepatotoxicity
what is the migration level of PTFE (polytetrafluoroethylene) into food?
low
what are MRLs?
maximum residue limits
EPA sets limits for how much pesticide can remain on food
these limits are known as tolerances (MRLs)
common chemical constituents in fabric softeners?
quaternary ammonium compounds
pthalates
synthetic musks
detrimental respiratory effects of exposure to chemical constituents in fabric softeners?
asthma
sensory irritation
pulmonary irritation
airflow limitation
what are you exposed to with dry cleaned clothes?
elevated levels of tetrachloroethylene (PERC)- a type of VOC
health effects of exposure to tetrachloroethylene (PERC)?
developmental
neurological
respiratory
what is the known additive in vaccines that is a concern?
aluminum (increases shelf life)
what does OSHA stand for?
Occupational Health and Safety
what does MSDS stand for?
Material Safety Data Sheets
what is the Fourth National Report on Human Exposure to Environmental Chemicals?
CDC report using data from National Health and Nutritional Examination Survey to assess levels of environmental chemicals in a U.S. subsample
utilizes blood and urinary markers
what are the main systems affected by VOCs?
hematological, nervous & immune systems
oncogenic in nature
where do you find benzene? health effects?
find in forest fires, volcanoes, part of crude oil, gasoline, exhaust, cigarette smoke
causes cells not to work effectively, marrow suppression, anemia, leukemia
where do we find toluene? who likes toluene? how much more potent than benzene?
find in smell of pain thinner, added to gasoline to improve octane ratings, used as a solvent
abused as an inhalant: this is what huffers are after (paint and glue)
25x more potent than benzene
where do you find xylene? main health effect? what can it penetrate?
used in histology labs, occurs naturally in coal, petroleum and wood tar
main effect: CNS depression
can penetrate most clothing
characteristics of phenol? what is it used in? what is it a precursor to?
white, volatile crystalline solid, produced from petroleum
used in conversion of precursors to plastics (used in plywood, construction, automative and appliance industries)
precursor to many drugs
oral anesthetic in chloraseptic/carmex but considered quite toxic PO
where might you find formaldehyde? health effects? URT vs LRT effects?
extremely common to find in adhesives, glues and dyes, pressed wood products, carpet, particle board, plywood, paper products, “wrinkle-free” clothing
health effects: mostly respiratory, mucous membrane, URT but not LRT (solubility prevents access to LRT)
where might you find vinyl chloride and PVCs?
health effects? what can it specifically cause?
“new car smell,” pipes, insulation, siding, shower curtains
off-gasing and leaching can cause hepatotoxicity, specifically causes hepatic angiosarcoma
what is vinyl chloride disease?
Raynaud’s (vasospasm of distal extremities)
acroosteolysis (dissolution of terminal phalanges and SI joint)
scleroderma-like skin changes (tightening)
what are PAHs? what are they made up of (physical make-up as well as byproduct of what)?
polycyclic aromatic hydrocarbons
multiple conjoined benzene rings
from combustion of carbon based fuel
two classes of toxic PAHs? make up of each? sources of each? health effects of each?
low molecular weight: 2-3 rings, exposure from home-based combustion, mothballs; can cause hemolytic anemia, heightened concern for people with known anemic conditions
high molecule weight: 4-7 rings, by-product of carbon combustion, major component of tar- from charred/grilled food, most carcinogenic substance in tobacco smoke
what was the first carcinogen to be discovered?
bezno(a)pyrene
what do benzo(a)pyrenes form?
heterocyclic amines
what are 5 ways to protect against exposure to PAHs?
- quit smoking
- don’t grill meat
- eat more brassicas (indole-3-carbinol, isothiocyanate)
- antioxidants
- marinade meats you want to grill in an acidic base such as vinegar or lemon
what is continine? how to test for it?
metabolite you can use to test for 2nd or 3rd hand smoke
used to measure tobacco consumption
test in the urine most commonly but can also use blood, saliva and hai r
where do you find asbestos? characteristics? 3 adverse health effects?
found in fire-proofing, insulation, friction products, tile
size of particulate matter is extremely fine: 0.01 millimeter thick, 3-20 millimeter long fibers, component of PM10 and 2.5
3 adverse health effects: asbestosis, mesothelioma, lung CA
what are the safest plastics? safer? un-safe?
safest plastics: #2, 4- no leeching or detection in humans
safer: #1, 5-some leeching, no detected health effects
un-safe: #3, 6, 7- known leeching, known health effects
what # is PVC? where do you find it? what can it contain? health effects?
polyvinyl chloride is a #3 plastic
find in plastic pipes, insulation, vinyl siding, IV bags and tubing
some contain pthalate
health effects: statistically significant increased risk of CV and nervous sys dz
what # plastic is in transvaginal mesh and diapers?
polypropylene (#5)
what are phthalates? concern? health effects?
used as a plasticizer (to soften)
concern is that it leeches easily
health concern: endocrine disruptor
LD50 (lethal dose) of polystyrene? what can acute and chronic exposure cause? other health concerns with polystyrene?
styrene itself is a weak toxin
LD50= 500-1000mg/kg
acute exposure can effect mucous membranes and respiratory irritation
chronic exposure can cause dizziness, fatigue, N/V, cognitive and perceptual loss, neural toxicity, possibly renal and hepatic toxicity
possibly/potentially a human carcinogen
oral exposure to polystyrene nanoparticles can affect iron absorption
where can you find bisphenol A (BPA)? health concern?
find in food packaging, metal can coating
endocrine disruptor b/c it is a xenoestrogen
species of black mold?
stachybotrys chartarum
air quality index- how does the EPA grade it?
color-coded and numeric scale (6 levels)
green–> maroon; 0-500
major sources of air pollution? smaller sources?
major sources: power plants, refineries, transportation
smaller sources: nail salons, dry cleaners, auto body shops
classification system of particulate matter?
PM10: all particles are less than or equal to 10 microns, anything bigger will not usu be deposited in the lungs
sources of PM2.5 particles; where can they go? main cause of what?
PM2.5: fine fraction particles
directly from combustion sources and formed secondarily from gaseous precursors of sulfur dioxide, nitrogen oxides, organic compounds
remain in atmosphere days to wks and travels through atmosphere hundreds and thousands of kms
main cause of reduced visibility (haze) in the US!!!
sources of PM10-2.5; where can it travel to?
PM10-2.5= coarse fraction particles
tend to deposit to the earth w/in mins to hrs and w/in tens of kms from emission source
health concern with ultrafine, less than 0.1 microns, particulate matter?
can leave the lungs and travel through blood to other organs, including the heart
definition of acid rain? caused by what? what can it lead to?
any form of wet precipitation with pH less than 5.6
caused by fossil fuel emissions: S and NOs combine w/H2O in the atmosphere
when environment can’t neutralize= damage!
accelerates the decay of buildings
changes aquatic ecosystems
forest soils lose nutrients
what is smog made up of? how is it formed? 5 components of smog?
mixture of air pollutants including gases and fine particles, often seen as a brownish yellow or grayish white haze in the air formed in earth's lower atmosphere when pollutants from cars, refineries, power plants, etc react chemically in the presence of sunlight components of smog: 1. ground level ozone 2. nitrogen oxides 3. VOCs 4. sulfur dioxide 5. particulate matter
6 criteria pollutants?
clean air act requiring EPA to set standards for the following:
- carbon monoxide
- particulate matter
- lead
- nitrogen dioxide
- ozone
- sulfur dioxide
how is ground level ozone created?
not emitted directly into the air but created by chemical reactions b/w oxides (NOx) and VOCs in the presence of sunlight
what kind of pollutant is ground levels ozone?
secondary pollutant b/c it is the result of two substances acting w/e/o
what is the problem with carbon monoxide exposure? ssxs? high levels outcome?
RBCs have a greater affinity for CO than O2 so CO displaces O2, which can lead to tissue necrosis and death
ssxs: H/A, dizziness, N/V, chest pain, confusion
high levels can lead to LOC and death
what is the main cause of haze?
PM2.5= fine fraction particles
primary cause of acid rain?
sulfur dioxide
make-up of chlorofluorocarbons? characteristics? commonly found where?
consists of chlorine, fluorine and carbon
very stable in troposphere
move to the stratosphere and broken down by strong UV light which releases the chlorine atoms that break down the ozone layer
commonly found in refrigerants, solvents and foam blowing agents
EPA is trying to phase out it’s use
what are CFCs being replaced by? and why?
hydrochlorofluorocarbons are replacing chlorofluorocarbons b/c they deplete the ozone less than CFCs (even though they still cause ozone depletion b/c they contain chlorine)
two main classes of pesticides?
organochlorine pesticides
acetylcholinesterase inhibitors
characteristics of organochlorine pesticides?
commonly used in past but many have been removed from market b/c of health and environmental effects and their persistence in the environment
DDT, chlordane, dieldrin, heptachlor
2 classes of acetylcholinesterase inhibitors? characteristics of each?
organophosphates: developed in early 19th century, used until 1930’s then realized main (=) health effects so instead started using it as a nerve gas in WWII, were popular in the 1970s again after ban on organochlorines, higher toxicity than carbamates
carbamates: salts or esters or carbamic acid
what is in fertilizer and what is the health effect it can cause?
nitrates in fertilizers
alters iron in Hgb from ferrous to ferric state which forms methemoglobin (abn Hgb) so RBCs lose ability to carry O2 to tissues
routes of exposure to heavy metals?
inhalation, ingestion, dermal absorption
what is LD50? lower the number means what? good to measure what? problems with LD50?
LD50= median lethal dose (dose given all at once that causes 50% of test group to die)
the lower the LD50 the greater the toxicity
great way to measure short-term acute poisoning
problems: wide variation btw species, animal rights concerns
5 mechanisms of heavy metal toxicity?
- enzyme/cofactor inhibition or potentiation
- disruption of membrane and other transport processes
- disrupt mitochondrial fxn= fatigue
- decreased neural fxn and nerve conduction
- bind sulfhydryl groups on proteins and a.a.s
potential sources of lead? jobs, hobbies, products that involve lead?
pre-1978 homes w/deteriorated lead paint
dust, paint, soil
imported remedies, cosmetics, miniblinds, metal wicked candles
jobs: smelting/mining, construction/remodeling, car repair, plumbing, police/military
hobbies: painting, stained glass, pottery glazing, soldering, shooting, making bullets, slugs, or fishing sinkers
products: computers, solder, pewter, ceramic glaze, jewelry, auto batteries, imported or older pre-regulation products
who is at most risk w/lead exposure?
children, infants and PG women (fetus)
ssxs of lead toxicity?
mb asx impaired abilities may include: decreased learning and memory lowered IQ decreased verbal ability impaired speech and hearing fxns early sxs of hyperactivity or ADHD
ssxs of low level lead toxicity?
myalgia, parasthesia, mild fatigue, irritability, lethargy, occ abd discomfort
ssxs of moderate level lead toxicity?
arthalgia, general fatigue, difficulty concentrating, muscular exhaustibility, tremor, H/A, diffuse abd pn, vomiting, wt loss, constipation
ssxs of severe level lead toxicity?
paresis, paralysis, encephalopathy, seizures, lOC, coma, death, lead line on gingival tissue, colic
best way to test/screen for lead?
blood lead
adult levels should be less than 20 mcg/dL
children should have levels less than 5 mcg/dL
what may imaging show if someone has lead poisoning/exposure/toxicity?
abd: may reveal lead items swallowed by small child
long bones: lead lines if significant exposure
where can you find mercury? major source of exposure? released into the air how? main type we are exposed to via a food source and what is the food source?
find mercury in thermostats, thermomemters, sphygmanometers, barometers, dental amalgams, fish
inhalation of elemental mercury volatilized from dental amalgams is a major source of exposure!
released into the air by combustion of fossil fuels, solid waste incineration, mining and smelting (can then deposit on land and in water)
methylmercury from fish is also another major exposure route
what can large amounts of methylmercury ingestion via fish cause? how is it transported to the brain?
damage to nervous system, infants born w/cerebral palsy b/c it can cross the BBB and placental barriers
high uptake in the brain= potent neurotoxin and teratogen, not fat soluble so transported to the brain by binding to cysteine, Hg ends up taking methionines place in membrane transport system
how is methylmercury created?
metabolism of elemental mercury by micoorganisms in sediment creates methylmercury which bioaccumulates in aquatic and terrestrial food chains
main source of methylmercury is in fish
methylmercury is highly absorbable in the GI tract and gut flora may also make methylate elemental Hg to make methylmercury
how is ethylmercury formed?
when body breaks down thimerosal (vaccine preservative)
good news is it is excreted from the blood more quickly than methylmercury
what is inorganic mercury? where can you find them?
category of mercury compounds including mercuric chloride, mercuric sulfide
found in batteries, some disinfectants, some health remedies and skin lightening creams
bioaccumulation vs biomagnification?
bioaccumulation: accumulation of substances in an organism
biomagnification: as you move up the food chain, concentration increases
how can you detox from mercury exposure?
NAC
BUT if you know there is a potential for repeated exposure to mercury don’t give NAC b/c it helps transport methionine into the brain which is the same mechanism mercury uses to get into the brain, instead give glutathione directly
predominant use of cadmium? other sources? when might absorption of cadmium be increased?
predominantly found in battery manufacturing but also found in pigment production, coatings, plastic stabilizers
cadmium absorption might be increased in iron deficiency
where is arsenic found? where is it absorbed best?
medicines, cosmetic lighteners, paint pigments, industrial wood preservation
absorbed well from GI tract, less so through inhalation, poorly absorbed through skin
best way to test for acute exposure to heavy metals?
blood
metals are cleared rapidly and accumulate in storage depots
how can hair testing be used to determine heavy metal exposure? pros and cons?
detects recent exposure (~last 3 mos)
can be 200-300x more concentration than in blood or urine therefore can give falsely elevated high levels
pros: godo for evaluation methylmercury, cheap and easy to perform, when performed properly can provide a qualitative screening test for exposure to heavy metals, CDC, EPA , ATSDR all recognize validity of hair mercury levels as indicator of maternal and fetal exposure to methylmercury
cons: only a screen, no indication of net retention, highly vulnerable to external contamination, no standard process for cutting, washing and analyzing hair, not reliable for testing elemental Hg, Cd or Pb
depuration vs detoxification?
depuration: action or process of freeing something of impurities, preferred term for removal of xenobiotics by the body
detox: process of transforming a toxic substance into non-toxic substance
what is a xenobiotic?
chemical compound that is foreign to the body, or to an entire biological system
what is nasal fatigue?
that you become accustomed to a smell the more you are around it
effect of starvation on NADPH and why it might not be a good idea for biotransformation?
NADPH is one component of phase 1 detox
generation of NADPH and UDP-glucuronate (phase 2) are closely connected to carb metabolism in the liver
under normal circumstances, in a well-fed state, the pentose phosphate pathway provides sufficient NADPH for biotransformation
increased biotransformation stimulates the PPP which shifts intermediates of malate and G6P to NADPH generation from gluconeogenesis
BUT in starvation NADPH for biotransformation can only be produced at the expense of gluconeogenesis…
main CYP in the liver? inhibitors of CYP?
CYP450-3A4
inhibitors: heavy metals, trauma, obesity, LPS, inflammation
what happens to glutathione production/regeneration with heavy metal poisoning?
glutathione is on a circadian clock: nadir at 6 pm
GSH cycles btw oxidation and reduction
if heavy metal is present, replenishment cannot occur= deficiency in GSH
3 types of absorption of xenobiotics?
simple diffusion, passage through pores, specialized transport systems
3 major sites of absorption of xenobiotics?
ingestion: GI, mostly the SI
inhalation: lungs
dermal: skin (worse w/eczema, soaking in water)
major storage sinks?
adipose, bones, liver, KDs
what are some of our barriers to toxic exposure?
BBB, placenta
what is the main idea of biotransformation?
conversion of lipid soluble xenobiotic into polar water soluble for excretion
3 routes of excretion?
urinary, biliary, pulmonary
Th1 vs Th2 responses?
Th1: mainly following infxn w/intracellular bac and some viruses; IL-2, INF-gamma, TNF-b; activates MOs, responsible for cell mediated immunity, phagocyte responses, proinflammatory, perpetuates AI response
Th2: mainly following infestations by GI nematodes; IL-4, IL-5, IL-10, IL-13, strong ab production, eosinophil activation (eosinophilic response in atopy), PG is Th2 dominant so as to not reject the baby (need to dampen Th1 response); inhibition of several MO fxns
how do toxins cause immune deficits?
hypersensitivity rxns including allergy
AI
what 3 things can cause atrophy and/or cell death of cells of the thymus?
DES, dioxin, DDT
exposure to what can make people more prone to allergic response?
PCB exposure
exposure to what can cause decreased splenic and thymic activity?
PAH exposure
exposure to these two items causes a decreased ability to kill candida
lead and mercury
by supplementing with what mineral can you provide protective immune fxn upon cadmium exposure?
selenium
what is an endocrine disruptor? examples? what is a xenoestrogen? phytoestrogen?
chemical that interferes w/body’s endocrine system and can produce adverse responses; example is DES (reproductive problems)
xenoestrogen: type of endocrine disruptor that imitates estrogen, can be natural or synthetic
phytoestrogens: xenoestrogens from plants
what substances affect female fertility? what two chemicals affect sperm production?
females: decreased w/PAHs, chemotherapeutic agents, solvents, BPA, particulate matter
males: organophosphates and heavy metals affect sperm production
what is the problem with PCBs and the thyroid?
PCBs look like thyroid
what two exposure hx forms did we review?
Crinnion
ATSDR
before doing any heavy metal specific testing what do you need to do?
run a CBC, CMP, lipid panel, complete UA, urine HCG for women, G6PD if planning to ever tx w/high dose Vit C, TB (if no recent one on file)
what is the best test to determine accurate body burden of heavy metals
there isn’t one..
pros of hair testing for heavy metals? cons?
pros: when performed properly can provide a qualitative screening test for exposure to heavy metals, but cannot diagnose metal toxicity, good for evaluating methylmercury, CDC, EPA, ATSDR all recognize validity, detects recent exposure (~last 3 mos), cheap and easy to perform
cons: once bound in hear metals will not be re-exchanged back into body= levels may seem to be extremely high (200-300x’s higher), only a screen, will need to confirm with blood or urine test, not an indication of body burden, hair is highly vulnerable to external contamination, no standard for washing, cutting, analyzing hair, not reliable for testing elemental Hg, Cd, or Pb
who may be a good candidate for stool testing?
pediatric population
what are the best binding affinities of chelating agents for mercury? best way to deliver chelating agents? side effects?
Hg2+ is the best followed in order by Ag2+ (silver), CH3+Hg1+, Cu2+, Cd2+, Pb2+, Zn2+
best to give IV
SEs: low systemic and local toxicity, generally well tolerated, can decrease systemic essential minerals, higher doses may cause CV reactions, elevations of liver transaminases, allergic reactions have been seen in some
DMPS: Hg, 3-5 mg/kg of body wt, IV best but can do PO too
DMSA: Pb, 20-30 mg/kg of body wt, oral on empty stomach
EDTA: Pb even though it has a better affinity for Hg, 50 mg/kg of body wt,
why do you need to avoid seafood (esp shellfish) in 1 wk prior to challenge testing?
shellfish or seaweed must be avoided for 1-2 wks before challenge so as to avoid a false elevation of arsenic or mercury (1/2 life for arsenic is ~7 days, methyl Hg clears in ~70 d from the body)
how is testing done for acetylcholinesterase pesticide exposure? specifics of testing? different %ages mean what?
test whole blood and plasma samples
test for RBC cholinesterase, whole blood (is considered true cholinesterase b/c it is identical to acetylcholinesterase found in synapse)
test for plasma cholinesterase (considered pseudo form b/c not identical to synapse form but it is easier to test for)
15-20% depression in cholinesterase means slight poisoning has happened
25-30% drop means more moderate poisoning
35-50% means more severe poisoning
what is the theory behind colon hydrotherapy?
increases bile dumping
with better bile excretion more toxins stored in the liver and GB are able to move into the intestines for excretion
can decrease the amount of toxins being recycled in the GI tract
can also help remove toxic bile which can irritate the GI tract
how can low temp saunas help with removing toxins?
how to do?
increase lipolysis, toxins can be stored in fat (storage sink)
helpful for excretion of some amount of heavy metals, solvents, plastics, pesticides, etc.
very important to work up to the 1 hr
low temp allows pt to tolerate longer time
7 supplements/foods that can help increase glutathione production and help in removal of toxins?
cysteine (L-cysteine, NAC) glutathione (not absorbed orally well) cruciferous veggies dietary fiber undenatured whey protein dietary fiber onions and garlic
4 basic supportive supplements?
vit C
fiber
selenium
zinc
health effects of cadmium? where does it accumulate? what does this cause? what problems then arise when you try and remove cadmium from the body? what two other diseases can it secondarily cause?
accumulation in liver and KDs (binds to metallothionein) which leads to renal tubular and glomerular damage and eventually causes irreversible proteinuria and progressive reduction in GFR, problem b/c if KD damage then chelation might cause more damage
can also cause osteomalacia and osteoporosis b/c it is increases urinary excretion of calcium and phosphorous= decreased hydroxylation of vit D metabolites
also causes severe pneumonitis, changes in lung fxn consistent w/emphysema, associated with lung CA
