Lecture 13: Solvents and VOCs Flashcards
Technically a _____ is any liquid that will dissolve a solute (e.g.,
water!)
solvent
for toxicology, solvents are…
organic compounds that are liquid
(think industrial solvents). Many different types.
organic solvents are often…
volatile
Lipophilic
Non-polar (therefore not water soluble)
May be natural or xenobiotics
Major route of exposure is inhalation, ingestion and sometimes skin
what solvent are humans exposed to most? (most likely)
ethanol! from alcohol consumption
Some people have a slow ADH -> risk of __________.
* Example of a resistance factor.
* Some people have an ALDH mutation -> risk of __________.
* Some people have slow forms of both ADH and ALDH -> higher risk of
________.
risk of alcoholism
risk of acetaldehyde-induced
stomach cancers
risk of alcoholism and FAS (Fetal Alcohol Syndrome)
tolerance of ethanol:
whats an example of tolerance in humans?
excessive drinking increases the
expression of the metabolic enzymes that
process ethanol (ADH, ALDH) in the liver. So
heavy drinkers can process alcohol more
efficiently compared to a non-drinker.
* Quicker at eliminating the toxicant.
_______: When a prior exposure to a toxicant alters the
metabolism or physiology of the organism so
that subsequent exposures to the same
toxicant result in a reduced effect
tolerance of an individual
how does the genetics of a person affect the toxicity of ethanol?
A mutation in the
mitochondrial form results in
only having an active
cytosolic isoform.
* Leads to higher levels of
acetaldehyde accumulation,
which is toxic.
how does the genetics of an individual determine our processing of ethanol?
Humans have two
aldehyde
dehydrogenases (one
cytosolic, one in the
mitochondria).
Most acetaldehyde is
processed by ALDH2 in
the mitochondria of the
liver
_____ causes a large range of effects in the brain:
* It readily moves into membranes, which can change their fluidity.
* ______ is a gamma-amino butyric acid (GABA) receptor agonist.
* GABA receptors function in dampening neuronal signaling (sedative
effect).
* ______ is an antagonist for NMDA receptors.
* May contribute to short-term memory loss
Ethanol
______ can also activate GABA
receptors, leading to sedation.
Used as a recreational drug and
found naturally in some beers
and wines
Gamma-hydroxy butyric acid
(GHB)
T/F; GABA binding releases Cl- into the neuron, leads to inhibition of signal, how ethanol dampens neuronal signalling
true
T/F: alcohol-related liver disease is a major cause of death
true, in addition to accidents while under the influence
what are the three main effects of ethanol?
fatty liver
cirrhosis
FAS
______ from ethanol: > 5% fat deposits in the liver (can also occur through other
metabolic syndromes like high blood pressure or glucose levels,
weight, triglycerides and cholesterol)
Fatty liver
_____ from ethanol: necrosis and fibrosis of liver cells
Cirrhosis
T/F: Ethanol induces CYP2E1, which can enhance the metabolism of other toxicants
(this can be good, or bad if it leads to metabolically activation of a compound).
true
T/F: GABA is our primary inhibitory signalling molecules
true
_________: estimated to affect <3% of births in
Canada.
Depends on:
1. How often alcohol is consumed
2. How much alcohol is consumed
3. Stage of pregnancy when alcohol is consumed
May be caused by the following during
development:
i. Production of reactive oxygen species
ii. Inhibition of NMDA receptors
iii. Alteration of genes involved in retinoic acid
signaling
Fetal Alcohol Spectrum Disorder
(FASD)
learning disabilities
* low birth weight
* difficulty understanding
the consequences of
actions
* depression
* obsessive-compulsive
disorder
* physical disabilities such
as kidney and internal
organ problems
* skeletal abnormalities
these are some of the symptoms caused by….
fetal alcohol spectrum disorder
ethanol binds to the gaba receptor, changes conformation, which causes gaba to bind even better, which causes the _____
inhibitory effect
T/F: Ethanol classified as a Group 1 carcinogen
true
Acetaldehyde metabolite is a weak mutagen and carcinogen.
* CYP2E1 induction by ethanol increases metabolic activation of carcinogenic
compounds.
* Ethanol can act as a solvent for some carcinogens, enhancing their absorption
into tissues of the upper GI tract.
* Additives and contaminants in alcoholic beverages that can influence
carcinogenicity.
* Also, carcinogenesis from alcohol and tobacco is synergistic.
these are some of the examples of why ethanol is classified as a….
carcinogen
what are some other problems caused by ethanol? other than its carcinogenic effects
Immune function is suppressed by alcohol.
* Absorption and bioavailability of nutrients are reduced by alcohol.
But ethanol may be beneficial in small amounts. 1 serving a
day may be actually good for you (i.e., hormesis)!
_______ is initially metabolized by the same alcohol
dehydrogenase that initiates the metabolism of ethanol
Methanol
______ converts formaldehyde to formate,
which is metabolized to carbon dioxide in folate-dependent reactions.
* Speed of the conversion depends on the species
* The slowest conversion… formate levels increase in the blood.
Formate can affect oxidative phosphorylation, causing production of
ROS and leading to apoptosis.
formaldehyde dehydrogenase
A sign of ______ poisoning is blurred vision or blindness caused by
formate. Eye damage can be permanent if the dose is high enough.
methanol
antifreeze = _____
ethylene glycol (1,2-dihydroxyethane)
what is the most important exposure route for ethylene glycol?
ingestion
accidentally swallowed or on purpose (cheap substitute for ethanol)
what are the 3 stages of acute antifreeze poisoning?
inebriation
cardiopulmonary
kidney toxicity
the ___ stages of acute antifreeze poisoning occurs after an asymptomatic period, during which it is metabolized
three
(1)- _____ of antifreeze
- Duration and degree
depends on dose
Inebriation stage
2) ______- of antifreeze
- 12-24 hours after exposure
- Tachycardia (fast heart rate)
which may progress to
cardiac failure and pulmonary
edema (due to oxalic acid)
Cardiopulmonary stage
T/F: antifreeze poisoning Also uses the same
enzymes involved in
alcohol metabolism
true
(3) ______ of antifreeze
- 24-72 hours post-exposure
- Due to precipitation of
calcium oxalate.
Kidney toxicity stage
______: Aromatic hydrocarbon.
* Produced naturally by fires or by human
activity.
* 1 to 2% of gasoline
* Component of cigarette smoke
benzene
High-level benzene
exposure results in an
increased risk of _________ = type of blood
cancer
acute
myelogenous leukemia
(AML)
Chronic exposure to
______ reduces the
numbers of red and white
blood cells and platelets
produced by bone marrow
benzene
T/F: Benzene must be
metabolically
activated by
CYP2E5
false, CYP2E1
Remember that ethanol induces
______. So drinking before
benzene exposure speeds up
this process
CYP2E1
_________-
are considered to be main
toxic metabolites of
benzene. These are
reactive molecules that
can form adducts to
proteins and DNA
o- and p-benzoquinones
where does benzene breakdown happen? (two possible places)
in the liver, or bone marrow
where were high-levels of benzene recently found? what products? after being exposed in 2024! already!
acne treatments, contained more than 800x more than the restricted amounts of benzene set by FDA
was from the benzoyl peroxide mostly, some from impurities (but not to the same extent)
_____:
very common solvent used in paints, lacquers, thinners,
glues, etc.
* Readily absorbed via inhalation
* Accumulates in brain and adipose tissue
* Metabolism occurs mostly in liver
toluene
Symptoms of inhalation of _______ (low to moderate levels):
tiredness, confusion, weakness, drunken-type actions, memory loss,
nausea, loss of appetite, and hearing and color vision loss
toluene
________:
Inhalation of many solvents
including toluene is inebriating.
Like alcohol, thought to interact
with GABA, NMDA and serotonin
receptors. High potential for abuse.
Solvent abuse is a public health
problem in some communities
Teratogen - produces syndromes
very similar to FASD.
Generalized solvent
encephalopathy
what are the three possible mechanisms by which toluene abuse affects the brain?
lipid solubility
oxidative damage
iron dysregulation
_______:
Toluene accumulates in myelin-
rich white matter, disrupting
membrane integrity
Lipid solubility
_______:
Free radicals from toluene
metabolism induce neuronal and
glial cell death
Oxidative damage
________:
Secondary demyelination leads
to abnormal iron deposition in
deep gray matter
Iron dysregulation
T/F: Unclear whether chronic, low level exposures to solvents have any deleterious effect
(a.k.a. ‘painters syndrome’ or chronic solvent encephalopathy).
true
Carbon tetrachloride (CCl4) is a…
halogenated hydrocarbon
_________:
* Xenobiotic used as a solvent, cleaning agent,
fire extinguisher, synthetic intermediate, grain
fumigant, and human anthelmintic.
* Its use has steadily declined since the 1970s.
* Forms free radicals (ROS) that acutely
damage liver cell components.
* CCl4 appears to be ubiquitous in ambient air, generally at low background levels
and it is still found in some water wells and
waste sites.
Carbon tetrachloride (CCl4)
Drycleaning is often done using ‘PERC’, what is it?
tetrachloroethylene
________:
* Readily absorbed in the lungs and GI tract.
* Liver toxicity: Metabolized by P450’s to PERC
oxide, which can trigger the generation of ROS
* Kidney toxicity: metabolites can damage kidney
cells and decreases in renal activity.
* In rats, PERC has been shown to induce cancer
in kidney cells.
* Human epidemiology studies have suggested
some association between esophageal cancers
and PERC exposure. But no cause and effect
relationship has been shown
PERC
_____ is an example where
humans are less
susceptible than rodent
models.
* We absorb _____ less
than rats and don’t
have the same
enzymatic activity to
convert it to its more
toxic forms
PERC
do solvents contaminate groundwater?
yes absolutely
Solvents are commonly found in many groundwater aquifers. The most common that
are monitored are ________ (4)
benzene, toluene, ethylbenzene and xylenes (referred to as “BTEX”)!!
Municipal water systems commonly use chlorine as a disinfectant (a great marker of
wastewater effluents), which can produce _______ as a by-product, a
known rodent carcinogen. Usually, the levels of solvents in water systems are well
below any potential toxic levels (usually <25 ppb). Toxicity starts occurring in the
ppm range.
chloroform (CHCl3)
_______ are compounds that easily
become gases or vapors
Volatile organic compounds (VOCs)
what are the sources of VOCs in indoor environments?
“Off gassing” of new building
materials and furniture.
Warm interior of video display units
(~60°C) produce “hot electronics
smell” caused by toluene, styrene,
and cresol volatilized from circuit
boards.
High temperature (~190°C) and
pressure (~30,000 N/m2) inside
photocopiers causes VOCs to be
released from toner and paper
T/F: VOCs are a bigger problem in outdoor evironments
false, bigger issue inside buildings (depends on ventilation and air turnover)
T/F: Ventilation can help reduce VOC exposure
true
Higher _____:
ventilation system or air
purifier can move more air
through a space per minute
potentially leading to faster
removal of VOCs and other
pollutants.
CFM
CFM = _______
Cubic feet per minute
what are the three common smells that are actually VOCs
“new car smell”
air fresheners
perfumes and colognes (PCPs)
T/F: “green” products release basically as many VOCs than normal products
true!! chemicals don’t have to be specifically listed in ingredients for normal household products… can call any mixture “fragrance”
T/F: solvents are not the same as VOCs but many solvents are VOCs
true!!
T/F: we can reduce VOCs with adequate air flow
true!!
Excellent air quality= ____
Good air quality= ____
Fair “= _____
poor “= _____
> 50
30-50
15-20
<15
how to calculate cfm/person
just divide cfm by people in room
