Chapter 9: Solvents

Question 1

What solvents are humans most likely exposed to?

Answer 1

Humans are likely exposed to ethanol more than any other solvent

Question 2

What are the enzymes involved in the metabolism of ethanol?

Answer 2

The enzymes involved in the metabolism of ethanol are Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase (ALDH).

Question 3

What is the intermediate product of ethanol metabolism?

Answer 3

Acetaldehyde is the intermediate product of ethanol metabolism.

Question 4

What is the end product of ethanol metabolism?

Answer 4

Acetate is the end product of ethanol metabolism.

Question 5

What is the risk of having a slow ADH for some Caucasians and African descendants?

Answer 5

Having a slow ADH increases the risk of alcoholism for some Caucasians and African descendants.

Question 6

What is the risk of having an ALDH mutation for some Asian descendants?

Answer 6

Having an ALDH mutation increases the risk of acetaldehyde-induced stomach cancers for some Asian descendants.

Question 7

What is the risk for some Hispanic populations who have slow forms of both ADH and ALDH?

Answer 7

Some Hispanic populations who have slow forms of both ADH and ALDH have a higher risk of alcoholism and Fetal Alcohol Syndrome (FAS).

Question 8

What are the effects of ethanol in the brain?

Answer 8

Ethanol causes a large range of effects in the brain, including changing membrane fluidity, functioning as a GABA receptor agonist, and contributing to short-term memory loss.

Question 9

What is the function of GABA receptors?

Answer 9

GABA receptors function in dampening neuronal signaling, which leads to a sedative effect.

Question 10

What is the relationship between ethanol and NMDA receptors?

Answer 10

Ethanol is an antagonist for NMDA receptors, which may contribute to short-term memory loss.

Question 11

What happens when GABA binds to its receptors?

Answer 11

When GABA binds to its receptors, it releases Cl- into the neuron, leading to inhibition of signal.

Question 12

What is GHB and how does it affect the brain?

Answer 12

Gamma-hydroxy butyric acid (GHB) can also activate GABA receptors, leading to sedation. It is used as a recreational drug and found naturally in some beers and wines.

Question 13

What is a major cause of death related to alcohol consumption?

Answer 13

Alcohol-related liver disease is a major cause of death.

Question 14

What is fatty liver?

Answer 14

Fatty liver is a condition where there are more than 5% fat deposits in the liver. It can also occur through other metabolic syndrome diseases.

Question 15

What is cirrhosis?

Answer 15

Cirrhosis is a condition where there is necrosis and fibrosis of liver cells.

Question 16

What is the role of CYP2E1 in ethanol metabolism?

Answer 16

Ethanol induces CYP2E1, which can enhance the metabolism of other toxicants. This can be either good or bad, depending on whether it metabolically activates a compound or not.

Question 17

What is Fetal Alcohol Syndrome (FAS)?

Answer 17

Fetal Alcohol Syndrome is estimated to affect 1% of births and can cause a range of physical and mental disabilities.

Question 18

What are the factors that determine the severity of Fetal Alcohol Syndrome?

Answer 18

The severity of Fetal Alcohol Syndrome depends on genetic background (ALD and ALDH variants), ethanol exposure during pregnancy, and the nutritional status of the mother.

Question 19

What are some of the physical and mental disabilities associated with Fetal Alcohol Syndrome?

Answer 19

Fetal Alcohol Syndrome can cause learning disabilities, low birth weight, difficulty understanding consequences of actions, depression, obsessive-compulsive disorder, physical disabilities such as kidney and internal organ problems, and skeletal abnormalities such as facial deformities.

Question 20

What are some of the hypotheses about what causes Fetal Alcohol Syndrome?

Answer 20

Hypotheses about what causes Fetal Alcohol Syndrome include reactive oxygen species, inhibition of NMDA receptors, and alteration of genes involved in retinoic acid signaling.

Question 21

What is the classification of ethanol as a carcinogen?

Answer 21

Ethanol is classified as a Group 1 carcinogen.

Question 22

What is the synergistic effect of alcohol and tobacco in carcinogenesis?

Answer 22

Carcinogenesis from alcohol and tobacco is synergistic.

Question 23

What are some other problems associated with alcohol consumption?

Answer 23

Alcohol can suppress immune function and reduce the absorption and bioavailability of nutrients.

Question 24

What is the effect of ethanol-induced CYP2E1 induction on other toxicants?

Answer 24

Ethanol-induced CYP2E1 induction can enhance the metabolism of other toxicants, which can be beneficial or harmful depending on whether it metabolically activates or detoxifies the compound.

Question 25

How is methanol initially metabolized?

Answer 25

Methanol is initially metabolized by the same alcohol dehydrogenase (ADH) that initiates the metabolism of ethanol.

Question 26

What converts formaldehyde to formate in methanol metabolism?

Answer 26

Formaldehyde dehydrogenase converts formaldehyde to formate in methanol metabolism.

Question 27

What is a sign of methanol poisoning?

Answer 27

A sign of methanol poisoning is blurred vision or blindness caused by formate.

Question 28

What can happen to the eyes if the dose of methanol poisoning is high enough?

Answer 28

Eye damage can be permanent if the dose of methanol poisoning is high enough.

Question 29

What is the last reaction in methanol metabolism and why is it important?

Answer 29

The last reaction in methanol metabolism is the conversion of formate to carbon dioxide. This reaction is slow in primates than rodents, and formate levels increase in the blood. Formate can affect oxidative phosphorylation, causing production of ROS and leading to apoptosis.

Question 30

What is benzene?

Answer 30

Benzene is an aromatic hydrocarbon that is produced naturally by fires or by human activity. It is also a component of cigarette smoke and 1 to 2% of gasoline is benzene.

Question 31

What is the increased risk associated with high-level benzene exposure?

Answer 31

High-level benzene exposure results in an increased risk of acute myelogenous leukemia (AML), a type of blood cancer.

Question 32

What happens with chronic exposure to benzene?

Answer 32

Chronic exposure to benzene reduces the numbers of red and white blood cells and platelets produced by bone marrow.

Question 33

What is the main toxic metabolite of benzene?

Answer 33

o- and p-benzoquinones.

Question 34

How is benzene metabolically activated?

Answer 34

Benzene must be metabolically activated by CYP2E1.

Question 35

What is the role of ethanol in benzene exposure?

Answer 35

Ethanol induces CYP2E1, which speeds up the process of metabolically activating benzene.

Question 36

What are o- and p-benzoquinones?

Answer 36

o- and p-benzoquinones are reactive molecules that can form adducts to proteins and DNA, and they are the main toxic metabolites of benzene.

Question 37

What are the common uses of benzene?

Answer 37

Benzene is a very common solvent used in paints, lacquers, thinners, glues, etc.

Question 38

What are the effects of inhaling toluene?

Answer 38

Inhalation of toluene in low to moderate levels can cause tiredness, confusion, weakness, drunken-type actions, memory loss, nausea, loss of appetite, and hearing and color vision loss.

Question 39

What is generalized solvent encephalopathy?

Answer 39

Generalized solvent encephalopathy is a condition caused by inhalation of solvents, including toluene, that can be inebriating and interact with GABA, NMDA, and serotonin receptors, resulting in confusion, memory loss, nausea, and other symptoms.

Question 40

What is the potential for abuse associated with solvents like toluene?

Answer 40

Solvents like toluene have a high potential for abuse, similar to alcohol, and can be a public health problem in some communities in Canada.

Question 41

Can chronic, low level exposures to solvents like toluene have any deleterious effect on the brain?

Answer 41

It is unclear whether chronic, low level exposures to solvents like toluene have any deleterious effect on the brain, a condition sometimes referred to as ‘painters syndrome’ or chronic solvent encephalopathy.

Question 42

What is carbon tetrachloride and what is its effect on the liver?

Answer 42

Carbon tetrachloride is a xenobiotic used as a solvent, cleaning agent, fire extinguisher, and other purposes, and is a ‘classic liver toxicant’. It forms free radicals that acutely damage liver cell components.

Question 43

What is tetrachloroethylene and what are its toxic effects on the body?

Answer 43

Tetrachloroethylene, often used in dry cleaning, is readily absorbed in the lungs and GI tract and can have toxic effects on the liver and kidneys. It is metabolized by P450’s to PERC oxide, which can trigger the generation of ROS, and metabolites can damage kidney cells and decrease renal activity. It has also been shown to induce cancer in kidney cells in rats and has been associated with esophageal cancers in human epidemiology studies.

Question 44

What is ethylene glycol?

Answer 44

Ethylene glycol is a constituent of antifreeze, de-icers, hydraulic fluids, drying agents, and inks, and is used to make plastics and polyester fibers.

Question 45

How is ethylene glycol exposure usually caused?

Answer 45

Ethylene glycol exposure usually occurs through ingestion, either accidentally swallowed, used in suicide attempts, or used as a cheap substitute for ethanol.

Question 46

What are the 3 stages of acute poisoning caused by ethylene glycol

Answer 46

The 3 stages of acute poisoning caused by ethylene glycol are: (1) a period of inebriation, the duration and degree depending on dose; (2) a cardiopulmonary stage 12-24 hours after exposure, characterized by tachycardia (fast heart beat), which may progress to cardiac failure and pulmonary edema (due to oxalic acid); and (3) kidney toxicity stage 24-72 hours post-exposure due to precipitation of calcium oxalate.

Question 47

What are the most common solvents found in groundwater aquifers?

Answer 47

The most common solvents found in groundwater aquifers are benzene, toluene, ethylbenzene and xylene (referred to as “BTEX”).

Question 48

What is chloroform and how is it produced in municipal water systems?

Answer 48

Chloroform is a known rodent carcinogen produced as a by-product when chlorine is used as a disinfectant in municipal water systems. It is a great marker of wastewater effluents.

Question 49

What are volatile organic compounds (VOCs)?

Answer 49

Volatile organic compounds (VOCs) are compounds that easily become gases or vapors.

Question 50

What are the sources of VOCs in indoor environments?

Answer 50

The sources of VOCs in indoor environments include the “off-gassing” of new building materials and furniture, warm interior of video display units, high temperature and pressure inside photocopiers, “new car smell”, air fresheners, and personal care products.