Solvent toxicity review

Question 1

General principles of solvent tox

Answer 1

CNS depression increases as length of carbon chain increases (more than 5 are not volatile enough).
solvents can extract fat from cell membrane (greater the molecular size, more functional groups, or more unsaturated)

Question 2

Categories of solvent-induced encephalopathy

Answer 2

Type 1: sx only that are reversible (fatigue, memory impair, difficult concentration)
Type 2A: sustained personality or mood change
Type 2B: cognitive function impair (may not be reversible)
Type 3: dementia

Question 3

PNS toxicity of n-hexane (metabolite of), MnBK, carbon disulfide

Answer 3

first in lower extremities.
Early sensory impair and parethesia.
later motor impair and denervation atrophy

Question 4

TEC (trichloroethylene) exposure

Answer 4

TCE-contaminated ground can release vapor to surface.
Drinking water is considered safe.
Water at tape is almost always below MCL.

Question 5

TCE toxicity

Answer 5

acute: resp depression and cardio.
Probably carcinogenic.
Liver cancer in mice but not rats. Kidney CA in male rat only. Lung CA in mouse but not rat (TCE metabolized to TCA and chloral in Clara cell).

“direct extrapolation from rodent data would overstate human TCE cancer risk.

Question 6

TCE metabolism

Answer 6

metabolites are more toxic.

Mostly oxidized via P450 (phase 1), some conjugated with GSH (phase 2)

Question 7

Organic solvents

Answer 7

CNS depressant: carbon tetrachloride > chloroform > vinyl chloride.
Carbon tetrachloride and chloroform are liver toxins.
vynyl chlordie and methylene chloride are carcinogen.

Question 8

Benzene toxicity

Answer 8

acute: CNS depression and arrhythmia. dermatitis, PE.
chronic: aplastic anemia, leukimia, carcinogen

Question 9

toluene tox

Answer 9

more powerful narcotic than benzene. not known to cause blood disorders.
reproductive toxin and teratoxin.

Question 10

Ethanol toxicity

Answer 10

irritant and CNS depressant.
Fetal Alcohol Syndrome.
Not neurotoxic like methanol

Question 11

EtOH metabolism

Answer 11

ethanol to acetaldehyde by alchol dehydrogenase.

acetaldehyde to acetic acid by aldehyde dehydrogenase

Question 12

Methanol exposure

Answer 12

industrial/household solvent, antifreeze, voluntary

Question 13

Methanol tox

Answer 13

blindness, gastritis, acidosis, seizure, death

Question 14

Methanol metabolism

Answer 14

methanol to formaldehyde slowly (by alcohol dehydrogenase).
formaldehyde to formic acid by aldehyde dehydrogenase rapidly.
Formic acid is toxic

Question 15

Methanol tx

Answer 15

sodium bicarbonate, folic acid (formic –> CO2 and H2O), ethanol (competing for same enzyme), fomepizole (inhibits alcohol dehydrogenase)

Question 16

Ethylene glycol (antifreeze) Metabolism

Answer 16

uses alcohol dehydrogenase.
acidosis.
oxalate binds to calcium causing hypocalcemia and tissue injury.

Question 17

Ethylene glycol toxicity

Answer 17

kidney damage, gastritis, vomiting.

hyperventilation, seizure, comma, arrhythmias, PE, cerebral edema.

Question 18

Ethylene glycol tx

Answer 18

lavage. sodium bicarbonate, formepizole or ethanol, folic acid, pyridoxine, thiamine

Question 19

Propylene glycol

Answer 19

SAFE!!

Question 20

Glycol Ethers

Answer 20

reversible spermatotoxicity and developmental toxicity

Question 21

Formaldehyde

Answer 21

regulated by OSHA as a nasal carcinogen. also causes sensitization.

Question 22

Phenols

Answer 22

rapidly absorbed through skin. extremely irritating/burns.

Cytotoxic to all cells and tissue.

Question 23

Regulatory status

Answer 23

PEL (permissible exposure level–law by OSHA).

TLV: threshold limit value (industry standard)