HSCI 560 Final (Air Pollution, Nanotoxicology, Reprodcutive Toxicology, Toxic Effects of Solvents and Vapors)

respiratory

air pollution is more than a _____ issue; it can shorten lives and is a T6 RF for CVD

• systemic

• cardiovascular

• CNS

• birth outcomes

what other systems/effects can air pollution have (other than respiratory)

1) Ozone

2) Sulfur dioxide

3) Nitrogen dioxide

4) Carbon monoxide

5) Lead

6) PM

what are the 6 EPA criteria pollutants

carbon dioxide

recently, there’s been a push to add what compound to the EPA criteria pollutants

national air ambient quality standards (NAAQS)

under the Clean Air Act, the EPA is required to set what, in order to protect public health from exposure to the pollutants

nonattainment

areas that exceed the NAAQS are designated as what

NAAQS

nonattainment areas must institute air pollution control programs to

reduce air pollution to levels that meet the what

• remove patient from the site of exposure

• maintain respiration by giving oxygen

• administer oxygen (100% or hyperbaric chamber)

• cardiac monitoring

• COHb levels 30-40% or 25% with symptoms require monitored setting and acid-base evaluation

• COHb above 40% require transfer to hyperbaric facility

what are treatment steps for carbon monoxide toxicity

valleys

in places like _____, warm airs can trap cooler air under it, leading to a temperature inversion

temperature inversion events

warm air trapping cold airs is dangerous and builds up dangerous concentrations leading to what

India (Dehli/Ahmedabad)

what country has the worst pollution in the world (w/mostly PM_2.5 and 13/20 pollutants)

China

what country has considerable pollution (w/mostly PM₁₀ and 46/100 pollutants)

• an umeployed, alcoholic, homeless man

• 3 men planned to murder him to obtain life insurance; they tried to kill him by feeding him anti-freeze (methanol) with his alcohol (ethanol), running him over, and freezing him but failed

• boarding house and CO poisoning is what killed him

who was Mike Malloy

the methanol in the anti-freeze was most likley cancelled out by the ethanol in the alcohol

how did Mike Malloy survive the anti-freeze and excessive alcohol consumption

1) at least 1 dimension in the nanoscale (<100 nm)

2) must be synthesized

3) when synthesized in bulk, must have uniform characteristics

what main 3 requirements do you have to meet in order to be classified as an engineered nanomaterial

a soccer ball is to earth as a carbon nanoparticle is to a soccer ball

what is an example of the concept of nanosize?

COVID-19

what type of vaccine is lipid nanoparticle enabled

it uses LNPs as a delivery system; the LNPs carry mRNA inside of them and deliver them to the cells

how does the COVID-19 vaccine used lipid nanoparticles (LNPs)

F

T or F: we can make blanket statements (generalizations like all nanoparticles are safe, toxic, behave in same way, etc.) about toxicity

Nanoparticles come in many shapes, sizes, coatings, materials, charges, structures, and behaviors

why can’t we make blanket statements about the toxicity of nanoparticles

inhalation, results in deeper deposition into lungs, translocation, and frustrated phagocytosis due to aspect ratios

what is the primary route of exposure to nanoparticles in occupational and environmental settings

size bc smaller nanoparticles can enter the body more easily and travel further to produce stronger toxic responses; Kim et al. 2015 shows that smaller nanoparticles cause higher oxidative stress and Aldossari et al. 2015 shows that smaller nanoparticles induce more hemolysis

Which property do you believe is of the most toxicological importance and why?

characterization

what is the first step in a toxicology study

agglomeration

particles loosley stick together; reversible

aggregation

particles are tightly bound/fused; can’t go “back down” (NOT reversible)

• Diverse properties

• Number of nanomaterials being produced

• Numerous routes of exposure

• Nanoparticles have large surface areas that are hydrophobic, allowing for the association of dyes, cell culture micronutrients, and cytokines thereby interfering with assays

• Bind contaminants such as LPS resulting in false positives

• Dosimetry issues (Do you expose based on mass, surface area, particle number?)

• Limited exposure assessment making it difficult to set relevant experimental exposure concentrations

• The nanoparticle-biocorona

• Interdisciplinary nature of nanotoxicology

why is studying nanotoxicology challenging

reproductive

the following describes what kind of toxicology:

defined as a delay in pregnancy, an increase in early pregnancy loss, or sub-fertility or absolute infertility, resulting from an exposure to a physical, biological, or chemical agent that alters reproductive performance of either partner or the couple (focus is on the parents)

developmental

the following describes what kind of toxicology:

defined as an alteration in the structure or function of a developing embryo, fetus, infant, child, or adult resulting from an exposure to the male or female either before or after conception or during development (focus is on the offspring)

endogenous reporductive hormones

in pharmaceutical settings, you need to be careful bc if a drug has too much similarity to _________, it can disrupt the reproductive cycle

alligators

what animals had abnormally small penises and low testosterone levels, due to endocrine disrupting chemicals found in Florida lakes

wallabies

what animals had reduced penis lengths (by 20%) as a result of endocrine disrupter and herbicide, Atrazine, in Australian water

number of sperm and volume of semen, sperm motility, sperm morphology

when we talk about male fertility, what factors are we taking into account

2-5 mL

what is the volume of semen

20 million/mL

what is the typical number of sperm cells

50% progressive

what’s a good percentage of sperm motility

30% normal

what’s a good sperm morphology percentage

procarbazine

what is an alkylating agent that’s used as a chemotherapy medication

it adds alkyl groups which leads to DNA damage and death of diving germ cells, leading to permanent death

how does procarbazine result in cell death

yes bc the spermatagonia are still there (can regen sperm production)

is procarbazine sterility reversible

Sertoli

boric acid targets what kind of cells

permanent

boric acid sterility is

semen

what is the most accessible and reliable for measuring biomarkers in terms of toxicity in males

vaginal and cervical secretions

what is the best biomarker for women in terms of specificity and relevance

synthetic progesterone and estrogen

birth control pills are made out of what

small

does it take a small or large amount of synthetic progesterone and estrogen to inhibit the ovulation

GnRH

progesterone in the pills inhibits this entire ovulation process, mainly by stopping the release of what

FSH and LH

progesterone leads to lower GnRH, leading to decrease of what hormones by the anterior pituitary

follicular development

decreased FSH inhibits what

synthetic progesterone; progesterone lvls are usually high only after ovulation

specifically what part of birth control pills tricks the body into thinking ovulation has already happened

Nonoxynol-9

what is the primary chemical used in spermicides that inhibits sperm motility

inhibits sperm motility by stopping sperm from traveling to the egg, resulting in immobilization and death

how does Nonoxynol-9 work

nourishes developing sperm cells

what do Sertoli cells do

lipid

solvents tend to accumulated in ____-rich tissues

1) number of C

2) whether it’s un/saturated, has dbl or trpl bonds between adj. Cs

3) configuration (straight, branched, cyclic)

4) halogenated or not

5) presence of functional groups

toxicity of a solvent is based on what factors

volatility and lipophilicity

what are the 2 most important properties of solvents that govern absorption and deposition

1) they are smaller than adults

2) high hand to mouth activity

3) immune, reproductive, digestive, and CNS are still developing

why are children more sensitive than adults to exposures (list 3 reasons)

low

do humans have low or high capacity for metabolizing TCE through the GST/GSH pathway (that’s common in rats)

• rats are good at metabolizing TCE through the GSH pathway, which ultimately ends up producing very toxic metabolites before they can excrete it

• humans are not good at metabolizing TCE through the GSH pathway, and are better at it through the P450 pathway, creating safer metabolites that are excreted in urine

why do rats suffer from extensive kidney damage due to TCE damage, as opposed to humans

they have low levels of epoxide hydrolase

why do B6C3F1 mice show high levels of liver cancer as a result of TCE exposure

epoxide hydrolase usually metabolizes DCA and TCA, which will now accumulate, leading to activation of PPARalpha, eventually leading to rapid cell growth, oxidative stress, lipid peroxidation, DNA damage, apoptosis suppression, and TF activation

how does low levels of epoxide hydrolase affect B6C3F1 mice negatively

Clara

TCE is carcinogenic in mouse lungs bc mice have high amounts of what type of cells

TCE targets Clara cells, and the Clara cells metabolize TCE into chloral by CYP450s. With low ADH though, chloral cannot be converted to TCOH (a safer metabolite), leading to accumulation of toxic chloral and cell death

how does having high amounts of Clara cells affect mice lungs negatively

low ADH levels

in terms of TCE exposure in mice lungs, why can chloral not be converted into the safer TCOH metabolite

• dose would have to be perfectly measured for the person (weight, size, etc.)

• must form uninterrupted seal for 5 minutes

• very volatile (would have to immediately administer or else it’d evaporate)

• upon waking up, nervous system would likely be heavily impaired (ability to communicate and think properly would be damaged)

• there’s a a very small difference between the dose required to knock someone out and kill them

why doesn’t chloroform work the way it does in the movies?