Lecture 13: Solvents and VOCs Flashcards by Zoe Phillips

Technically a _____ is any liquid that will dissolve a solute (e.g.,
water!)

solvent

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for toxicology, solvents are…

organic compounds that are liquid
(think industrial solvents). Many different types.

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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

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what solvent are humans exposed to most? (most likely)

ethanol! from alcohol consumption

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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)

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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.

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_______: 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

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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.

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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

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_____ 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

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______ 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)

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T/F; GABA binding releases Cl- into the neuron, leads to inhibition of signal, how ethanol dampens neuronal signalling

true

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T/F: alcohol-related liver disease is a major cause of death

true, in addition to accidents while under the influence

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what are the three main effects of ethanol?

fatty liver
cirrhosis
FAS

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______ 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

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_____ from ethanol: necrosis and fibrosis of liver cells

Cirrhosis

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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

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T/F: GABA is our primary inhibitory signalling molecules

true

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_________: 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)

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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

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ethanol binds to the gaba receptor, changes conformation, which causes gaba to bind even better, which causes the _____

inhibitory effect

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T/F: Ethanol classified as a Group 1 carcinogen

true

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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

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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)!

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_______ 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