Unit 2 Flashcards
top 4 leading causes of death in developed countries
cancer
cardiovascular disease
Respiratory disease
chronic liver disease
human health issues in regards to organic compounds
lethality, cancer, respiratory disease, reproductive disease, birth defects, neurotoxic effects, metabolic diseases
evidence for human health issues caused by organic compounds
epidemiology, occupational exposures, accidents, in vivo and in vitro tests, etc
epidemiology
comparison of health and disease in different populations
factors that impact toxicity
dose, exposure period, mixtures, age, genetic make-up, diet, etc
how is age associated with toxicity
when toxicity can be observed
different stages of vulnerability
genetic differences may lead to difference among individuals in:
phenotypes, bioactivation, detoxification, repair
Diet and toxicity
source, immune response, health, etc
cancer
unrestrained proliferation of cells, invasion, metastases
carcinogen
substance that causes or induces neoplasia, new or autonomous growth of tissue (causes cancer)
can be parent compounds or metabolites
can be dose dependent
Neoplasm
lesion resulting from growth
biomarkers for exposure
something in the blood, urine, etc that has been linked to a cancer or chemical exposure
mission of IARC
to coordinate and conduct research on the cause of human cancer and the mechanisms of carcinogenesis to develop scientific strategies for cancer prevention and control
IARC categories
group 1, 2A, 2B, 3, 4
group 1
carcinogenic to humans
eg. benzene, Aflatoxin B1, benzo[a]pyrene B[a]P (found in cig smoke), and diethylstilbestrol
group 2A
probably carcinogenic to humans
group 2B
possibly carcinogenic to humans
group 3
not classifiable as to its carcinogenicity to humans
group 4
probably not carcinogenic to humans
cigarettes and smoking
lots of tobacco associated cancers
3000 chemicals in processed tobacco leaves
4000 identified chemicals plus unidentified chemicals when burned
60 known carcinogens in the smoke
Benzo[a]pyrene
organic and aromatic
comes from fossil fuels, forest fires and charred meat (do not eat)
maximum acceptable conc of 0.00004 mg/L (MAC)
metabolized by body enzymes
metabolite is carcinogenic and causes stomach tumors (interacts with DNA)
Benzene
aromatic hydrocarbon
MAC of 0.005 mg/L
important industrial solvent and precursor in the production of drugs, plastics, gasoline, synthetic rubbers and dyes
acute exposer can cause: dizziness, headaches and confusion
chronic exposure can cause leukemia and aplastic anemia
Leukemias
bone marrow is flooded with immature blood/blast cells
26% of all childhood cancers, hypothesized to be caused by environmental exposures
Aflatoxin B1
natural substance produced by fungus
LD50 0.01mg/kg
consumption can cause liver cancer
group 1
developmental toxicants
cause of 30-75% of miscarriages
number one cause of infant death
cause 2-3% major birth defects
result in 16-17% of abnormal neurological function
increased frequency of childhood cancers
Organic teratogens
a substance that causes birth defects
cigarette smoke
benzo[a]pyrene
pesticides (DDT)
PBDEs
dioxins
furans
PCBs
reproductive toxicity in males
reduction in sperm count and semen quality
increase incidence of testicular and prostate cancer, undescended testicles, various deformities of the reproductive tract
reproductive toxicity in females
breast cancer, endometriosis and clear cell carcinoma
Diethylstilbestrol
given to pregnant women to reduce risk of miscarriage from 1940-1971
caused clear cell carcinoma in the daughters of the women that took DES
endocrine disrupting chemicals
organic endocrine disrupting chemicals
bisphenol A, hydroxy-PCB, 4-alkylphenols, phthalates, DDT, and diethylstilbestrol
endocrine system
control system that responds to internal and external signals to maintain the bodies chemical equilibrium
regulates sexual development
hormones
used in signaling and regulatory mechanisms
cause 40% of cancers in women
hormone cycles can be disrupted by natural compounds
mechanisms of action of endocrine disrupting chemicals
mimic the effects of endogenous hormones
antagonizing the effects of endogenous hormones
altering the pattern of synthesis and metabolism of normal hormones
modify hormone receptor levels
Bisphenol A
organic and aromatic
plastic used in packing and bottles
group 3
limit exposure to susceptible populations (babies, rapidly dividing cells are more susceptible)
neurological deficits potentially caused by organic compounds
coma, convulsions, rapid death, Alzheimer’s, Parkinson’s, dementia, learning deficits and intellectual disabilities
as we age our ability to detoxify ____
decreases
inorganic elements may be natural___
toxicants
zinc
essential at low conc and not very toxic to humans
toxic to fish
Canadian soil guideline of 250mg/kg
canadian water guide line of 5000 ug/L
metal mine effluent regulation of 400ug/L
can be high in natural rock, soil developed over the rocks may also have high conc of metals and plants may uptake metals (pathway of exp)
arsenic
toxic to humans, even at low levels
children are more vulnerable due to lower body weight and tendency to play with soil
avg bio accessibility is 7.3%
oral absorption CSF is 2.8
selenium and fluorine
essential at low concentrations but toxic at high concentrations
mining
crushing rocks and exxposing them to O2 and H2O, metals are released, water may also be acidic
red staining indicates acid rock drainage
fluoride and human health
to little in drinking water results in dental cavities
to much results in dental fluorosis or skeletal fluorosis
ideal range for drinking water is 700-1500 ug/L
adding fluoride to water is controversial (other health effects, individual choice?)
speciation of metals and inorganic elements
the chemical form of the metal or inorganic element
affects toxicity
can refer to the valence or oxidation state
not always used in regulations because of the difficulty of analysis and cost
bioaccessible
the proportion of a chemical that is soluble in bodily fluids
affects risk
measuring bioaccessibility
measured using either in vivo or in vitro lab tests
in-vivo is expensive, long, difficult to apply to humans and ethically problematic
in vitro uses simulated bodily fluids
lead
occurs naturally in soil, water and rocks at very low conc
effects neurological damage, slowed growth and development, learning and behavior problems, hearing and speech problems in young children
prenatal exposure is also a concern
maximum acceptable conc in water is 10 ppb
Canadian soil quality guideline 70 ppm
modern sources of lead exposure
paint in older homes or exposed during renovations
some paints still contain lead
old water pipes and lead-based solder
ammunition
contaminated soil from industrial activities or mining
gold ore (ground at home in Nigerian homes)
arsenic sources
natural: ground water
anthropogenic: mining, pressure treated wood, pesticides, fungicide and rat poison
routes of exp for arsenic
ingestion of contaminated food or water
inhalation of contaminated soil or dust
dermal exp
Giant Mine
mine in Yellowknife caused inorganic arsenic pollution
first ten years: ore roasting released 20,000 tones of arsenic to surrounding areas (still there)
next 40 years: 278,000 tonnes of arsenic stored underground (plan is to freeze it permanently
clean up cost is 4.38 billion
calculating bioaccessibility
EDI (estimated daily intake) = (conc * exposure factors * bioaccessibility) / body weight
non carcinogenic Hazard quotient =
EDI/reference dose
carcinogenic incremental cancer risk (ICR) =
EDI * cancer slope factor (CSF)
human health risk assessment thresholds for arsenic
<210 mg/kg: permanent residents can live
210-8,300 mg/kg: recreational users can use
> 8,300 mg/kg: remediation required
REEs
rare earth elements
new potential toxicants
used for wind turbines, electric vehicles, electronics, etc.
one source is mining
no regulations in place yet for REE mining
risk can not yet be evaluated
metals and inorganic elements cane be ___ at low conc
essential
metals and inorganic elements can be _____ at high conc
toxic
LOD
lethal oral dose
organophosphate pesticides
low to moderate persistence and there fore toxicity might need to be high to extreme for it to be effective
three types: A, B and C
neurotoxicity through inhibiting acetylcholinesterase, which will happen in many non target organisms
organophosphate pesticides type A
used in controlled release
intermediate toxicity (LOD50 25mg/kg)
not stable enough for wide release (degrades before it can be effective)
organophosphate pesticides type B
mostly phased out
very toxic (LOD50 3mg/kg)
not very selective
responsible for many accidental deaths from exposure
organophosphate pesticides type C
fairly wide use
low toxicity LOD50 885 mg/kg
more toxic to insects because of their different metabolic pathways
controversy over long term health effects
acetylcholinesterase
enzyme that removes acetylcholine (neurotransmitter) after nerve signal is sent
if it is inhibited nerve synapses can not reset, organisms go into paralysis
Pyrethrins
a better approach to pesticides
isolated form chrysanthemums (natural plant defense)
not persistent
low toxicity to humans and mammals as they metabolize them extremely fast
can be used indoors and outdoors where stable enough
not used that much in agriculture
boost selective toxicity with additives like synergist (eg. PBO)
inhibit the sodium channel (neural toxicity)
synthetic Pyrethrins
commercial use
more stable
not persistent
human LD50 > 5000 mg/kg
PBO
inhibits metabolism in insects and in humans
makes Pyrethrin’s more efficient (increase bonding potential to sodium channels)
Herbicides
easier than other pesticides to make non-toxic to vertebrates/mammals/humans
Atrazine
triazine
interfere with photosystem II
used to control weeds among less sensitive plants
lower toxicity to animals as they do not have photosystem II
persists for months to a year
moderately water soluble
does not bioconcentrate ( log Kow = 2.7)
persistent in water and soil ( guide line is 2 ppb)
can and has contaminated groundwater
still used in north america
2,4-D and 2,4,5-T
non-persistent Herbicides
now being restricted
kills dicotyledons not monocotyledons (kills weeds while grass is left unaffected)
mimic auxin (chemical produced by plants to control growth)
low impact in the environment beyond where its sprayed
soluble
not persistent in soil or water
low toxicity to humans
some concern for persistence in clays and other types of soils
mixture of the two = agent orange
2,4,5-T
now banned because of Dioxin by products
2,4-D
currently in wide use
chronic exposure has been linked to non-Hodgkin’s lymphoma
IARC classification , group 2B
high risk to vulnerable groups (children)
users are required to have training and wear PPE
Glyphosate
non persistent herbicide
targets all plants
inhibits shikimic acid synthesis pathway
water soluble
no bioconcentration
does not migrate to ground water
degrade into harmless biproducts
low toxicity to humans ( LD50 > 4000 mg/kg)
claimed to be environmentally friendly
cosmetic use is banned - still want to limit exposure to users
controversy around glyphosate
some concern that peristence can occur in some compartments
some health concerns for direct exposure
IARC: probably carcinogenic
why is non-persistant pesticide use increasing
traditional and emerging mosquito-born pathogens
malaria, west Nile, zika
Neonicotinoid pesticides
used to protect seeds and crops against a range of insect pests
low toxicity to humans, birds and others
LD50 50-500 mg/kg
not persistent, breaks down in water and sunlight
can be persistent in soil but not mobile
most widely used pesticide globally
imidacloprid (Neonicotinoids)
controversy around neonicotinoids
toxicity to non-target insects
collapse of bee colonies
use is now restricted in many jurisdictions
unique example of pesticide restriction because of environmental impact rather than human health concerns
potable
drinking water
ground water
traditional source of drinking water
unsustainable use globally
surface water
never safe for drinking unless treated
unsustainable use in many global regions
drinking water
quality is important for human health
concern for pathogens and other biological contaminants (parasites, viruses, helminths, amoebas, etc)
most water pathogens cause gastro intestinal illness (2.1 billion are highly susceptible)
pathogen sources that affect drinking water
fecal matter from mammals or birds (main)
agricultural run off
manure and natural fertilizers
community sewage systems
septic systems
wildlife
water monitoring
to many pathogens to monitor all of them
test for E.coli as a fecal indicator because it correlates with most other fecal source pathogens
drinking water in low income communities
contamination is the main concern
800 mill with no access
1.3 billion with some access but not enough for all sanitation needs
80% of diseases are water related
34,000 deaths daily
drinking water in high-income communities
biological contamination is mostly controlled
rough 90 Canadians die annually from drinking contaminated water
Key factor in biological water contamination
lack of treatment technology
Walkerton
water treatment failure case
town in ontario, happened in May 2000
E.coli outbreak
2300 illnesses and 7 deaths
caused by agricultural runoff into a faulty well in combination with a broken chlorinator (no treatment)
contamination report was ignored by water operator
was reported by the hospital
need for on site water testing
conventional water tests are done in the lab and is usually a 1-3 day turn around
drinking water chemical contaminants in high income communities
linked to minimizing costs, taxes, government services and a global infrastructure deficit
result of a failure to monitor and and a poor distribution system
chlorine disinfection
treatment for biologically contaminated water
generally effective against pathogens
limit to how much we can add as the disinfection process produces disinfection byproducts (DPB’s)
DBPs
THMs: possible carcinogens and other genotoxicity, can cause methylation of DNA
new water treatment options
at tap: filters, ultraviolet and reverse osmosis systems
bottled water
environmental impact through energy and waste produced
bottled water
quality is better than tap water
less likely to have high THMs and known or unknown pathogens
still recommend tap water because it reduces the environmental impact (waste, plastic production, etc.)
benefits of choosing tap water
less of an environmental impact
better water governance ad accessibility
healthier ecosystems that provide fresh water
in the long term, overall health risks are probably lower compared to bottled water
Waste water and reuse
return treated sewage to the reservoir for drinking water
creates a “closed loop” for complete water recycling
Waste water and Antimicrobial-resistant infections
conventional method takes 4-5 days, high labor costs
implement for waste water before release to the environment
main sources of ionizing radiation
medical and natural (background radiation)
two types of radiation
non-ionizing and ionizing
non-ionizing radiation
low frequency
sources: power lines, radio and cell phones, microwaves, infrared, visible
Effects: Heat, excites electrons
ionizing radiation
high frequency
sources: ultra violet, x-ray, gamma ray
effects: breaks bonds, DNA damage
particulate radiation
type of ionizing radiation
Alpha particles: 2N and 2P, heavy, collide with matter and lose energy quickly, barely able to penetrate skin, a concern if inhaled or ingested
Beta particles: electrons, negatively charged, penetrate 1-2cm of water or human flesh
Neutrons: generated from splitting atoms in nuclear reactors, penetrate the furthest (concrete)
Electromagnetic Waves
type of ionizing radiation
Gamma rays: energy transmitted in a wave, penetrate greater than alpha and beta particles
X-rays: similar to gamma except they are artificially produced
natural radio activity
most elements are comprised of a mixture of isotopes a very small portion of which are unstable
the decay of unstable elements is radioactive
isotopes
variants of elements which have different number of neutrons but the same number of protons
radioisotopes
isotopes that are unstable and release energy as they decay
Tritium
3H
eg. of natural radioactivity
produced by the reaction of cosmic rays with atmospheric gases such as O2 and N
uranium
all atoms are mildly radio active
eg. natural radioactivity
decay series contains radon (222 Rn) and polonium (210Po)
Polonium
emits alpha particles
eg. natural radioactivity
Radon
radiactive gas found naturally in the environment
ubiquitous on earth
produced by the decay of uranium found in soil, rock and water
U-238 -> Ra 226 -> Rn 222
can enter a house through well or ground water, windows and cracks in the floor or walls
decay continues when inhaled into the lungs. emitted alpha particles damage lung tissue which may lead to cancer
200Bq/m^3
Bq
becquerel: one disintegration per second
Radon and human health
noted as a health problem when underground uranium miners died of lung cancer at high rates
risk of cancer development depends on conc and duration of exposure
years between exp and development of cancer
can cause skin, lung, bone tissue and bone marrow cancer
estimated that 16% of lung cancer deaths in Canada are a result of radon exp
sources of manufactured radiation
health sciences
nuclear weapons and power production
accidents
X-Rays
manufactured source of radiation
valuable imaging tool in medicine, research and security
uses small doses of radiation
SV
Sievert: measure of the health effects of low doses of ionizing radiation in the human body
therapeutic radiation
radiation treatment now used predominantly to treat cancer
historically used to treat non cancerous diseases before the risks were clear
causes either direct DNA damage or produces charged particles to damage DNA
can also damage normal cells
estimated cause of 5% of secondary cancers
Iodine - 131
travels in blood, used for imaging (low dose) and for treatment of thyroid cancer
ring worm radiation
from 1905-1960 X-rays were used for ringworm treatment of the scalp of children
estimated that 200,000 children were treated
caused an increased development of cancer in patients
nuclear weapons
source of manufactured radiation: use, testing and manufacturing
Hiroshima and Nagasaki
uranium-235 and plutonium-239
deaths in 1km radius of explosion
increased incidence of leukemia (peaked 5-7 years after)
nuclear power production
includes mining, uranium fuel fabrication, waste storage and disposal
environmental impact of nuclear power stations
process will warm waterways which changes the surrounding ecosystem
Chernobyl
April 25, 1986
131iodine, 134 and 137 cesium
caused acute radiation sickness (nausea, diarrhea)
increased thyroid cancer in children
clean up workers had high incidence of leukemia
Fukushima Daiichi
nuclear power plant
earthquake, March 11, 2011
caused a tsunami that disabled AC power and carried off fuel tanks for emergency generators
hydrogen explosion released radioactivity
131I and 137 Cs
radiation and tissues
different tissues vary in their sensitivity
most sensitive tissue are the gonads
least sensitive is the bone surface
fetus is most sensitive in the first trimester
physical DNA damage cause by ionizing radiation
single and double strand breaks
oxidized bases
base loss
genotoxic
toxic to genetic materials of an organism
properties of mercury
metallic and liquid at room temp
very useful which has resulted in its mobilization and wide spread contamination
can be both organic and inorganic
can be methylated by bacteria in soils and sediments
no biological function and is extremely toxic
monomethyl mercury
organic compound
accumulates and biomagnifies in the food chain
“Mad as a Hatter”
comes from the suggestion that hat makers were exposed to mercury
mercury poisoning causes trembling fits and neurotoxicity
occupational exposures to Mercury
ore mining, processing and purification
Historically used in the felt hatter industry
amalgamation process of silver and gold extraction
Mercury and gold mining
historical practice for the developed world and a modern practice for some developing countries
liquid Hg is used to amalgamate gold
artisanal gold mining
informal mining methid used by individuals or families
provides income for poor city dwellers
mercury gold mixture is heated in an open pan, releasing mercury vapors
is also released into river water which can then be taken up by fish which may be eaten by local communities
Minamata Japan
Widespread Mercury poisoning related to industrial waste
1932-1968
methylmercury was released into a bay
neurological disease in children
> 1700 deaths + more neurological damage
pathway was through shellfish and cats
Minamata disease
methylmercury poisoning
Chisso corporation (chemical company)
was making acetaldehyde using mercury as a catalyst which generated methylmercury
paid 86 mill in compensation
settlement reached in 2010
Ontario “Minamata”
first nations communities in NW Ontario were exposed to mercury in the 1960’s and onwards as a result of industrial pollution
Grassy Narrows
Mercury contamination
came from Dryden, a pulp and paper mill in the 1970’s owned by Domtar
used mercury in the production of caustic soda for bleaching paper
dumped 9000 kg of mercury into the English Wabigoon river
migrated >250 km down stream where it persists in sediments and is taken up by fish
previous owners were not charged for their pollution as part of a deal to sell the mill in 1979
cleanup and compensation cost around 85 mill
Clay lake
87 km downstream of dryden
mercury poisoning from the paper mill
mercury in adult walleye was 30 x the national average in 1970, 2-10 x in 2010
Remediation options for clay lake
focus is on reducing mercury in sediments
- wait for natural recovery
- add unpolluted sediment to dilute Hg conc
- add clay cap to cover contaminated sediments
- add activated carbon to bind Hg
- dredge the lake bottom
Organically bound mercury
methylmemrcury and dimethylmercury
most toxic forms
speciation is important
mercury’s toxicity
it is a neurotoxicant that effects young children and pregnant women
sources of Mercury
coal burning, Chlor-alkali plants, mercury mining and gold mining
runoff and inflow, settling, wet and dry deposition, emission and transport
most common exposure pathway to mercury for humans
fish
all mercury in fish tissue is methylmercury
consumption advisories are common
consumption advisory for fish
guide that indicates the maximum number of fish meals/ month
based on mercury and other contaminants found in fish
depends on region, species, size, age, and gender of each consumer
impact of consumption advisories
alternative foods will be used- which may be less healthy
advisory may be ignored (unknown effects)
impact on traditional way of life
guiding and other business opportunities for recreational fishing become unavailable (unemployment)
wildfires and HG
identified source in the mercury cycle
they release Hg from the soil into the atmosphere (Volatile element)
methylation and bioaccumulation
fires are increasing due to climate change
previously the main source of Hg in arctic organisms was thought to be long range transport of industrial emissions
GMO’s
genetically modified organisms
engineered genetic traits by transferring DNA from one living thing to another
no evidence to date that GMO’s are worse than crops modified by conventional breeding techniques
reasons to develop GMO’s
plant resistance to disease
improved nutritional value (increase of vitamin A in golden rice)
increased crop productivity
consumer appeal
improve human health
Bacillus Thuringiensis (Bt)
naturally occurring bacterium that produces crystal proteins that are lethal to insect larvae
protein inserts its self into the membrane of the gut epithelial cells and creates an ion channels through which ATP can be depleted
started to be used as a pesticide in the 1920’s
does not persist
needs to be converted from a protoxin to a toxin which requires alkaline pH and the resence of specific proteases found in the gut of insects (has to be ingested to be effective)
not toxic to mammals
registered as a pesticide in 1958
limitations of natural Bt
rapidly washed away by rain and degrade under the suns UV rays
does not effect insects that live within the plant or underground
other synthetic pesticides were readily available and often very efficient in killing insects so Bt was not widely used
Bt corn
registered with the EPA in 1996
GMO
DNA from Bt was put into corn
Og production of insulin
purifying the protein from the pancreas of cows and pigs
expensive, difficult and the insulin could cause allergic reactions
Insulin and GMO’s
once the structure of human insulin was identified in 1955, the cow and pig insulin could be chemically modified to be the same as human insulin
(review the process)
Benefits of GMO’s
reduced environmental impacts of spraying pesticides
increased agricultural yield
decreased frost damage
increased opportunity for beneficial insects
reduced exposure to pesticides for farm workers and other non-target species
more precise than traditional breeding techniques
overall cost reduction
decreased loss of critical habitat
efficient production of life saving medicines
environmental concerns of GMO’s
invasiveness
resistance
cross contamination
co-existence with traditional crops
potential for environmental impact
additional concerns regarding GMO’s
food safety
scientific information and accurate information
labeling (not required in Canada)
traceability
international and transboundary trade
Economic impacts
developed roundup
developed seeds that are round up resistant
substantial equivalence
if the GMO is significantly similar to the natural product its OK to use
GMO’s and food safety
DNA its self is not a concern
concern is for the transgenic introduction of allergenic protein
10-70 KDa
resistant to digestion
stable to heat processing
similar to amino acid homology in allergen binding sites
Star Link corn
Cry9c Bt toxin protein
EPA approved in 1998 but only for animal feed due to concerns for potential allergenic response in humans
in sept 2000 consumer group found it in taco shells
taco bell and safeway recall taco shells from supermarkets on sept 11, 2000
Crispr Cas9
clustered regularly interspaced short palindromic repeats
hallmark of bacterial defense system
gen editing tool
Cas9: DNA cutting enzyme
widely used for research in both eukaryotes and prokaryotes
more precise
He Jainkui
Chinese researcher
targeted CCR5 gene to prevent HIV-infection of 3 babies
questionable consent from parents
sentenced to three years in prison
